Home Synthesis, characterization, in silico and in vitro studies of novel glycoconjugates as potential antibacterial, antifungal, and antileishmanial agents
Article Open Access

Synthesis, characterization, in silico and in vitro studies of novel glycoconjugates as potential antibacterial, antifungal, and antileishmanial agents

  • Sher Wali Khan EMAIL logo , Saira Nayab , Muhammad Naveed Umar , Momin Khan , Anila Iqbal , Nasir Ahmad , Haroon ur Rashid , Muhammad Ishaq Ali Shah , Naila Gulfam , Muhammad Zahoor EMAIL logo , Riaz Ullah and Essam A. Ali
Published/Copyright: February 13, 2024
Download Article (PDF)
Open Chemistry
From the journal Open Chemistry Volume 22 Issue 1

Abstract

In the present work, several new glycoconjugates (8a–e) were generated from glycopyranosyl-α-trichloroacetimidates (sugar-OTCA) as glycosyl donors and dimethyl-l-tartrate as an aglycone acceptor in good to excellent yields. In the synthetic protocol, various monosaccharides were transformed into pentaacetylated derivatives and then into glycopyranosyl-α-trichloroacetimidates. Afterward, the sugar-OTCA was reacted with dimethyl-l-tartrate using Schmidt’s trichloroacetimidate protocol to give the desired products. The newly synthesized glycoconjugates were characterized by FT-IR, 1H, and 13C-NMR spectroscopic analytical methods. All the target compounds (8a–e) were tested in vitro against various strains of bacteria and fungi at different concentrations. The results revealed that the target compounds had encouraging antibacterial and antifungal potential. The antileishmanial activity of the target compounds against Leishmania tropica promastigotes was also investigated. The in vitro results were further supported by the in silico docking study that indicated minimum values of the docking scores and binding energies for the resulting complexes obtained by the favorable interactions between the target compounds (8a–e) and the selected strains of bacteria and fungi. The docking results proposed promising antibacterial and antifungal activities of the target compounds (8a–e) against the selected bacterial and fungal species.

Keywords: glycoconjugates; glycopyranosyl-α-trichloroacetimidates; glycosylation; antimicrobial; antileishmanial; molecular docking

1 Introduction

Carbohydrates (biomolecules) are often found attached to other biomolecules that constitute glycoconjugates. Glycolipids and glycoproteins are normally found on cell surfaces that act as receptors for cell–cell determination and are involved in cell growth, repair adhesion, migration, and tumor metastasis in cancer [1]. Vaccination is one of the most cost-effective ways and a key strategy for controlling various infectious diseases caused by viruses, bacteria, and parasites [2]. Polysaccharides and oligosaccharides can be antigenic [3], and capsular polysaccharides of bacterial pathogens, which include Streptococcus pneumoniae, Haemophilus influenzae type b (Hib), and Neisseria meningitides, are highly antigenic and can be recognized by mammalian B cell receptors. Capsular polysaccharides are major targets for eliciting carbohydrate biomolecule-specific antibody responses to provide protection from these pathogens. However, these molecules are poorly immunogenic, having a short-term immune response without immunological memory. The conjugation of biomolecules of these pathogens to protein carriers can induce long-term protection against encapsulated bacteria, opening a pathway for the development of glycoconjugate vaccines [3,4]. Synthetic glycans indeed possess a well-defined composition, providing reproducible biological activities with safe and better profiles. Synthetic oligosaccharides are helpful in elucidating the minimal structure of the microbial polysaccharides, referred to as epitope or antigenic determinant [5], which can ensure the bactericidal antibody production in sufficient amounts and with long-term protective immunity of the host. This step is very crucial for designing a new generation of improved and safer vaccines, either through a chemical method or from a bacterial source. Glycoconjugates based on chemically well-defined oligosaccharide frameworks are nowadays at the forefront of vaccine development and medication. The synthesis of complex glycans has made significant progress in the last few years. A number of synthetic approaches, such as green synthesis (solid-phase), one-pot programmable synthesis, and enzymatic and improved synthetic methods, have introduced a bucket of new elegant pathways for oligosaccharide antigens for immunological studies. Meanwhile, an improved strategy for structural determination based on X-ray crystallography, nuclear magnetic resonance, or in silico molecular docking studies, as well as advanced techniques for studying carbohydrate–protein interactions, i.e., glycoarray, surface plasmon resonance, and isothermal titration calorimetry has been extensively applied to predict the minimal structural requirements that are needed for the immunological activity of the oligosaccharides.

The synthesis of a glycoside is a common reaction in nature that provides numerous oligo-saccharides, glycoconjugates as glycolipids, glycoproteins, and glycopeptides. The structural variety of the oligo-saccharide portion is recently recognized. Oligo-saccharides are inherent in the variability of the glycosidic linkage and are perfect as carriers of life information and selectivity. Therefore, synthetic organic chemistry flourished rapidly in the past 25 years and focused on the preparation of oligo-saccharides for precise purpose such as in the production of antibodies, their screening, the specificity of selectin and lectin, interface investigations with germ [6,7] and bacterial receptors [8,9,10], as a substrate for glycosidases [11,12], glycosyltransferases [13], and as a probe in molecular recognition investigation, like conformational study. To date, it is a challenge for chemists to design glycosidic bonds with a high regio- and stereoselective control similar to those occurring in nature. Two diverse approaches are used for the construction of glycosidic bonds, i.e., enzymatic and chemical. Enzymatic glycosylation is largely based on explicit glycosyl-transferases that employ nucleoside monophosphate sugars or nucleoside diphosphates as donors. The nucleoside di- or monophosphate residues are the departing groups and carbohydrate sugars, or other aglycones are the acceptors [14]. The synthesis of oligo-saccharides is based on glycosylation via the union of several building blocks to make a glycosidic linkage. Generally, the donor molecule is synthesized by integrating a leaving group with the anomeric center of one properly protected glycosyl building block in most glycosylation reactions. Since the pioneering work of Koenigs and Knorr for the development of the glycosylation technique (1901) [15], the method has been adapted and is still in practice [16]. The glycosyl donors are typically halides, which are activated with silver or mercury salts. The superior modification uses glycosyl-fluorides as donor molecules [17,18]. To support a stereo-controlled SN2-type path, less polar solvents such as cyclohexane, dichloromethane, and petroleum ether are frequently utilized as reaction conditions. The relevance of this strategy led to exceptional outcomes such as the synthesis of numerous oligo-saccharides that include the blood groups (A-ve), B-ve, and Lea-determinants [19]. However, the key disadvantage of the Koenigs–Knorr method is the prerequisite for the smallest amount of the promoters and thermal volatility of some glycosyl halides. A widespread glycosylation scheme was designed by R. R. Schmidt and J. Michel in 1980, which avoided the use of heavy salts of metal as promoters [20]. O-Glycosyl trichloroacetimidates (sugar-OTCA) were synthesized and introduced as a new donor. The method is handy, adequately steady, and can be triggered for the glycosylation with small amounts of Lewis acids, such as BF3·Et2O, TMS-OTf, Sn(OTf)2, Ag-OTf, and ZnCl2·Et2O [21,22]. The configuration at the anomeric site, i.e., α or β of the trichloroacetimidate donors is vital for the anomeric stereo control of the glycosidic bond making. Moreover, β-trichloroacetimidates can be prepared with anhydrous potassium carbonate as a base [23] (kinetic control), while the use of sodium hydride, cesium carbonate, or potassium hydroxide [24] or with a phase transfer catalyst [25] entirely provided the α-trichloroacetimidates (thermodynamic control). Electron-deficient nitrile species are well acknowledged to endure straight and reversible base-catalyzed addition of alcohols to a triple-bond structure, hence giving O-alkylimidates [26,27]. Imidate synthesis has the benefit, as they can directly be obtained as stable adducts, which are slightly more susceptible to hydrolysis than parallel salts. Therefore, a base-catalyzed renovation of the anomeric oxygen into a good leaving group should be feasible, for example, by the addition to trichloro-acetonitrile (TCA). It is worth mentioning that the newly formed imidates have been utilized for the formation of oligo-saccharides, inositol derivatives, sphingosine, amino acids polycyclic and macrocyclic glyco-pyranosides [28,29,30,31]. Polycyclic or macrocyclic glycosides (anthracyclines, calicheamicin, macrolactones, etc.) have attracted great attention due to their antitumor and antibiotic properties [32,33].

The therapeutic potential of glycoconjugates has not been fully evaluated yet. Therefore, herein, we have synthesized glycoconjugates, designated 8a–e, utilizing glycopyranosyl-α-trichloroacetimidates (sugar-OTCA) as glycosyl donors and dimethyl-l-tartrate as an aglycone acceptor. The synthesized compounds were characterized using different spectroscopic techniques and were then evaluated for various therapeutic potentials.

2 Materials and methods

In the continuation of our studies to develop new pathways and for the synthesis of organic compounds [34,35], we herein account for a simplistic synthesis of some glycoconjugates, designated 8a–e, by using dimethyl-l-tartrate as an acceptor and glycopyranosyl α-trichloroacetimidates as donors (Scheme 1).

Scheme 1 Synthesis of acetylated monosaccharides (6a–e).
Scheme 1

Synthesis of acetylated monosaccharides (6a–e).

2.1 Synthesis of acetylated monosaccharides (6a–e)

In carbohydrate chemistry, and especially for the synthesis of various glycol-sides and oligo-saccharides, acetylated sugars are generally employed as simple intermediates, which are of low-cost and beneficial for designing numerous natural products containing glycosides, oligosaccharides, and other glycoconjugates. The most commonly used protocol for the acetylation of sugar alcohols employs an excess of acetic anhydride and pyridine [36]. Pyridine derivatives, such as 4-N,N-dimethylaminopyridine (DMAP) and 4-pyrrolidinopyridine, are added to the reaction as co-catalysts in some cases to expedite the reaction [37,38]. For the synthesis of sugar donors (Sugar-OTCA), first, we have selected five monosaccharides (d-glucose, d-galactose, d-mannose, d-glucosamine hydrochloride, and d-galactosamine hydrochloride), respectively, and were acetylated by using acetic anhydride in pyridine and a catalytic amount of DMAP to afford pentaacetylated compounds (6a–6e) in 70–78% yields (Scheme 1).

For the removal of some unreacted sugars, the acetylated sugars were purified through washing and column chromatography. Subsequently, their structures were confirmed by spectroscopic techniques. The IR data of the derivatives showed characteristics of CO stretching bands in the 1,738–1,733 cm−1 range in addition to CH stretching at 2,989–2,966 cm−1. 1HNMR spectroscopy confirmed both the formation of α and β-anomers in 3:1. The anomeric hydrogens appeared as doublet ranging from 6.35 to 6.31 ppm with coupling constants in the range of 4.0–3.7 Hz for α-anomers and from 5.66 to 5.58 ppm with coupling constant in the range of 8.4–8.0 Hz for β-anomers, respectively. Additionally, five singlets were observed in the range of 2.21–1.80 ppm with the integration of three protons each for five acetyl CH3 groups. In 13C-NMR, the peaks at 170.2, 170.3, 169.7, 168.5, and 168.2 ppm were assigned to the CO (acetyl) carbon of compounds (6a–e), respectively, those appearing in the range of 89.8–89.2 ppm were assigned to the anomeric carbons, and those observed at 20.3, 19.7, 19.5, and 18.9 ppm were assigned to the methyl carbons.

2.2 Synthesis of glycopyranosyl α-trichloroacetimidates (7a–e)

In glycosyl trichloroacetimidates, the anomeric oxygen atom was derivatized with an easily removable group, i.e., a good leaving group. This type of derivatization makes glycosyl trichloroacetimidates good glycosyl donors. They can be activated by Lewis acids like borontrifluoride-etherate BF3·Et2O or TMS-OTf for glycosylation reactions.

Five glycopyranosyl α-trichloroacetimidates were synthesized in 75–90% yields using pentaacetylated intermediates (6a–e) (Scheme 2).

Scheme 2 Preparation of glycopyranosyl α-trichloroacetimidates (sugar-OTCA).
Scheme 2

Preparation of glycopyranosyl α-trichloroacetimidates (sugar-OTCA).

The formation of glycopyranosyl α-trichloroacetimidates was initiated with chemo-selective elimination of the anomeric acetyl groups in compounds (6a–e) using a mild base, such as hydrazinium acetate. The resultant hemiacetals (sugar alcohol) were immediately reacted with a large excess of trichloroacetonitrile in the presence of 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU) as a catalyst [39,40]. The thermodynamically more stable α-anomers were synthesized. The corresponding β-anomers were not detected by 1H-NMR spectroscopy.

1H-NMR spectral data showed broad singlet peaks ranging from 8.63 to 8.59 ppm with the integration of one proton for the N–H groups. The anomeric hydrogens appeared as doublets ranging from 6.62 to 6.55 ppm with J-values ranging from 4.0 to 3.7 Hz. These coupling constants were in the range of axial equatorial and equatorial configuration of H-1 and H-2, and therefore, an α-trichloroacetimidate was assigned. In 13C-NMR, peaks ranging from 161.6 to 160.3 ppm were assigned to O–C–NH of acetimidates. The anomeric carbon atoms appeared in the range of 93.5–91.4 ppm.

2.3 Synthesis of glycoconjugates (8a–e)

After the successful synthesis of glycopyranosyl-α-trichloroacetimidates, they were used further as glycopyranosyl donors [39]. Glycoconjugates (8a–e) were prepared in 59–70% yields using dimethyl-l-tartrate as an acceptor (Scheme 3). Both the donor and acceptor were mixed in a 1:1 ratio.

Scheme 3 Synthesis of glycoconjugates (8a–e).
Scheme 3

Synthesis of glycoconjugates (8a–e).

The synthesis of glycoconjugates was also confirmed by spectral analysis. The IR data of 8a–e showed (OH) bands in the 3,423–3,411 cm−1 region in addition to CO stretching in the 1,746–1,732 cm−1 range, and CO–C bands in the 1,336–1,313 cm−1 range. In the 1HNMR spectra, characteristic doublets were confirmed for the N–H protons (8d–e) ranging from 6.98 to 6.93 ppm with J-values 9.5 Hz. The anomeric hydrogens were observed as doublets in the range of 5.69–5.46 ppm with J-values of 8.3–8.2 Hz, which confirms the formation of β-anomers. The coupling constant in mannose (a C-2 epimer of glucose) appeared at 3.7 Hz due to the axial-equatorial H-1–H-2 interaction. The α-anomers were not detected by 1HNMR spectroscopy. The mono-glycoconjugate formation was supported by the appearance of doublets in the range of 4.77–4.72 ppm, having J-values of 9.6 Hz, and 2.4 Hz for the chiral methine protons of dimethyl-l-tartrate carrying an OH group. Another doublet appeared in the range of 4.66–4.61 ppm with a J value of 2.4 Hz for the second methine hydrogen. In 13C-NMR spectra, the peaks in the 172.3–171.4 ppm range were assigned to CO (ester). The anomeric carbon atoms appeared in the 96.5–95.9 ppm range. Elemental analysis additionally supported the desired glycoconjugates.

2.4 Biological activities

2.4.1 Antibacterial assay

The agar well diffusion assay procedure was employed to determine the antibacterial potential of the target compounds [41,42]. Five bacterial strains, i.e., Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), Salmonella typhi (S. typhi), Acaryochloris marina (A. marina), and Pseudomonas aeruginosa (P. aeruginosa), were used in the experiment. The first nutrient broth medium was prepared by dissolving 0.4 g of the nutrient broth in 50 mL of distilled water, the pH was adjusted to 7.0, and autoclaved. The test compounds at three varied concentrations (dissolved in DMSO) were added to the wells of the Petri plates and incubated at 37°C for 24 h. The zone of inhibition of the test compounds was calculated after 24 h.

2.4.2 Antifungal assay

The agar well diffusion method was used to check the antifungal activities of the compounds against the clinical isolate of Candida albicans and Aspergillus flavus [41,42]. First, Sabouraud dextrose agar (SDA) was prepared according to the manufacturer’s instructions. The medium was then autoclaved at 121°C. After autoclaving, the medium was poured into Petri plates. A 0.5 McFarland standard was prepared by mixing 0.05 mL of 1.175% barium chloride dihydrate (BaCl2·2H2O), with 9.95 mL of 1% sulfuric acid (H2SO4). The test compounds in different concentrations (500, 250, and 100 μg/mL) were added to the wells of the Petri plates and incubated at 35°C for 48 h. The zones of inhibition of the test compounds were calculated after 48 h. The results were noted and elucidated accordingly.

2.4.3 Antileishmanil assay

The antileishmanial activity of glycoconjugates (8a–e) was determined by Zhai’s method employing a pre-established culture of Leishmania [43]. Triple-N media slants overlayed with 199 media were used for the parasite growth. Amphotericin B was taken as positive control and was also serially diluted in 199 media. Micro liter plates were incubated in a shaker incubator at 24°C for 72 h. The assay was performed in triplicate. After the incubation period, 20 µL was taken from each dilution and put in an improved Neubauer counting chamber and live parasites were counted under a microscope. IC50 values of compounds were calculated using Prism software [43].

2.5 Molecular docking studies

Molecular docking studies of compounds (8a–e) with the selected fungal and bacterial strains were performed using the latest PyRx v0.8 tool. The default setting in PyRx v0.8 is the Auto Dock Vina Wizard v4 [44]. The three-dimensional structural data of pathogenic proteins were downloaded in PDB format from the protein data bank of high resolutions (http://www.rcsb.org/pdb).

3 Results and discussion

3.1 Mechanism of targeted compound synthesis

The key benefits of the trichloroacetimidate methodology comprise the numerous prospects for stereo-control in the O-glycosidic bond construction. Exceptional stereo control may be attained by utilizing sugar-OTCA as a donor molecule carrying a participant neighboring group at the 2-site (neighboring group participation) in addition to carrying out the forward reaction, an appropriate mixture of solvents and catalysts (nitrile and ether effect). Nitriles are known for experiencing straight and reversible base-catalyzed addition of alcohols in the triple-bond system, thus giving an imidate [45,46] that can be directly separated as a stable product and less sensitive to breakage than the parallel salts. The selection of the catalyst and solvent pair in the glycosidic bond formation plays a vital part in achieving high stereoselectivity and stereo control at the anomeric position. Generally, if any masked group is present at the second position of the imidate donor site, the glycosylation reaction conforms to an SN2-type pathway in less or non-polar solvents utilizing weak acids and low temperatures. The effect of the reaction medium or solvent under SN1-type reaction conditions is of definite attention and widely considered for nitriles and ethers. In the case of diethyl-ether as a solvent, the SN1-type reaction is preferred by a potent acid catalyst such as TMS-OTf. Due to a reverse effect, the contribution of ethers yields equatorial oxonium ions, which support the formation of the α-glycosidic bond (thermodynamic control). The effect of nitriles is more complicated. The nitriles favorably attack the (α)-face of the greatly reactive carbenium ion intermediate to produce the α-nitrilium-nitrile conjugate (kinetically organized) and, consequently, yields the β-glycosidic linkage (Figure 1). Conversely, the thermodynamically stable β-nitrilium-nitrile conjugate yielded the α-glycoside [47,48,49,50].

Figure 1 Effects of ether and nitrile on the glycosylation reaction.
Figure 1

Effects of ether and nitrile on the glycosylation reaction.

3.2 Spectral details of the synthesized compounds

3.2.1 Procedure for the formation of glycopyranosyl-α-trichloroacetimidates (7a–e)

Trichloroacetonitrile (10 mL, 100 mmol) and DBU (2.81 mL, 20 mmol) were mixed with crude hemiacetals (3.48 g, 10 mmol) in dichloromethane (50 mL) under a nitrogen atmosphere by stirring at 0°C for 1.5 h. The progress of imitate formation was detected by TLC. The solvent was separated by a rotary evaporator under reduced pressure. The impure product obtained was purified by column chromatography (ethyl acetate:n-hexane (3:7) was used as an eluent).

3.2.2 2-3-4-6-Tetra,O-acetyl-α-glucopyranosyl-trichloroacetimidate (7a)

Yield: 83%. Yellow color oil. 1H-NMR (400 MHz, CDCl3): δ (ppm): 8.6 (bs, 1-H, N–H), 6.6 (d, J = 3.7 Hz, 1-H, H-1), 5.4, 5.3, 5.3 (3 pseudo t, J ∼ 8.1 Hz each one, 3-H, H-2, H-3, H-4), 5.5 (d.d, J = 11.9, 3.3 Hz, 1-H,H-6a), 4.43 (d.d.d. J = 10.4, 3.6, 2.1 Hz, 1-H, H-5), 4.8 (d.d. J = 11.9, 2.2 Hz, 1-H, H-6b), 2.1, 2.0, 2.0, 2.0 (4s, 12-H, 4 × CH3) (Figure S1). 13C-NMR (100 MHz, CDCl3): δ (ppm): 171.5, 169.7, 168.5, 169.2 (4, CO, of acetyl), 160.5 (O-CNH), 91.5 (C-1), 72.6, 71.7, 69.5,68.9 (C.2-C.5), 61.7 (C.6), 20.2, 20.1, 19.4, 19.3 (4 × CH3, acetyl) (Figure S2). Anal. Calc. for C16.H20.Cl3.NO10: C = 39.00; H = 4.09; Cl = 21.59; N = 2.84; O = 32.47; found: C = 39.03; H = 4.11; Cl = 21.57; N = 2.87; O = 32.50.

3.2.3 2-3-4-6-Tetra,O-acetyl-α-galactopyranosyl- trichloroacetimidate (7b)

Yield: 90%. Yellow oil.1H-NMR (400 MHz, CDCl3): δ (ppm): 8.6 (bs, 1-H, N–H), 6.6 (d, J = 3.9 Hz, 1-H, H-1), 5.4, 5.3, 5.3 (3-pseudo t, J ∼ 7.0. Hz each one, 3-H, H-2, H-3, H-4), 5.4 (d.d. J = 12.5, 3.6 Hz, 1-H,H-6a), 4.4 (d.d.d, J = 10.4, 3.6, 2.1 Hz, 1-H, H-5), 4.8 (d.d, J = 12.5, 2.1 Hz, 1-H, H-6b), 2.1, 2.0, 2.0, 2.0 (4s, 12 H, 4 × CH3) (Figure S3). 13C-NMR (100 MHz, CDCl3): δ (ppm): 171.8, 169.9, 169.6, 169.4, (4 × CO, acetyl), 160.3 (O-C-NH), 91.3 (C-1), 72.3, 71.6, 69.2, 68.1, (C, 2, C, 5), 61.6 (C, 6), 20.3, 20.2, 19.5, 19.2, (4 × CH3, acetyl) (Figure S4). Anal. Calc. for C16.H20.Cl3.NO10: C = 39.00; H = 4.09; Cl = 21.59; N = 2.84; O = 32.47; found: C = 39.04; H = 4.05; Cl = 21.57; N = 2.86; O, 32.50.

3.2.4 2.3.4.6-Tetra,O-acetyl-α-mannopyranosyl-trichloroacetimidate (7c)

Yield: 88%. Yellow brownish oil. 1H-NMR (400 MHz, CDCl3): δ (ppm): 8.6 (bs, 1-H, N–H), 6.6 (d, J = 3.7 Hz, 1-H, H-1), 5.4, 5.3 (2-pseudo t, J ∼ 5.9 Hz each one, 2-H, H-2, H-3), 5.3 (t, J = 8.9 Hz, 1H, H-4), 5.4 (d.d, J = 12.5, 3.6 Hz, 1-H,H-6a), 4.4 (d.d.d, J = 10.4, 3.6, 2.1 Hz, 1-H, H-5), 4.8 (d.d, J = 12.5, 2.1 Hz, 1-H,H-6b), 2.1, 2.0, 2.0, 2.0 (4s, 12-H, 4 × CH3) (Figure S5). 13C-NMR (100 MHz, CDCl3): δ (ppm): 171.3, 170.5, 169.6, 169.3 (4 × CO, acetyl), 160.6 (O-C-NH), 91.4 (C-1), 72.5, 71.2, 69.7, 68.5 (C-2-C-5), 61.5 (C-6), 20.2, 20.0, 19.7, 19.4 (4 × CH3, acetyl) (Figure S6). Anal. Calc. for C16.H20.Cl3.N.O10: C = 39.00; H = 4.09; Cl = 21.59; N = 2.84; O = 32.47; found: C = 38.98; H = 4.10; Cl = 21.57; N = 2.88; O = 32.50.

3.2.5 3-4-6, TriO-acetyl-2-acetamido-α-glucopyranosyl-trichloroacetimidate (7d)

Yield: 79%. Brown yellowish oil. 1H-NMR (400 MHz, CDCl3): δ (ppm): 8.6 (bs, 1-H, N–H), 6.6 (d, J = 3.8 Hz, 1-H, H-1), 5.4, 5.3 (2-pseudo t, J ∼ 8.5 Hz each one, 2-H, H-3, H-4), 5.4 (m, 1-H, H-2), 5.3 (d.d, J = 12.5, 3.6 Hz, 1-H, H-6a), 4.4 (d.d.d, J = 10.4, 3.6, 2.1 Hz, 1-H, H-5), 4.8 (d.d, J = 12.5, 2.1 Hz, 1-H, H-6b), 2.1, 2.1, 2.0, 2.0 (4s, 12-H, 4 × CH3) (Figure S7). 13C-NMR (100 MHz, CDCl3): δ (ppm): 170.8, 169.8, 169.4, 169.3 (4 × CO, acetyl), 161.3 (O-C-NH), 91.3 (C-1), 72.4, 71.2, 69.6, 68.7 (C-2-C-5), 62.5 (C-6), 20.4, 20.3, 19.5, 19.1 (4 × CH3,acetyl) (Figure S8). Anal. Calc. for C16H21Cl3N2O9: C, 39.08; H, 4. 30; Cl, 21.63; N, 5.70; O, 29.28; found: 39.05; H, 4.33; Cl, 21.60; N, 5.67; O, 29.26.

3.2.6 3-4-6,TriO-acetyl-2-acetamido-α-galactopyranosyl trichloroacetimidate (7e)

Yield: 75%. Yellowish oil. 1H-NMR (400 MHz, CDCl3): δ (ppm): 8.5 (bs, 1-H, N–H), 6.5 (d, J = 3.8 Hz, 1-H, H-1), 5.4, 5.3 (3-pseudo t, J ∼ 6.0.0 Hz each one, 3-H, H-3, H-4), 5.4 (m, 1-H, H-2), 5.3 (d.d, J = 12.5, 3.6 Hz, 1-H, H-6a), 4.4 (d.d.d, J = 10.4, 3.6, 2.1 Hz, 1-H, H-5), 4.8 (d.d, J = 12.5, 2.1 Hz, 1-H, H-6b), 2.1, 2.1, 2.0, 2.0 (4s, 12-H, 4 × CH3) (Figure S9). 13C-NMR (100 MHz, CDCl3): δ (ppm): 170.4, 169.9, 169.5, 169.3 (4 × CO, acetyl), 161.6 (O–C–NH), 91.7 (C-1), 73.3, 71.8, 69.8, 68.2 (C-2-C-5), 62.6 (C-6), 20.5, 20.4, 19.5, 19.2 (4 × CH3, acetyl) (Figure S10). Anal. Calc. for C16H21Cl3N2O9: C, 39.08; H, 4.30; Cl, 21.63; N, 5.70; O, 29.28; found: 39.05; H, 4.33; Cl, 21.60; N, 5.67; O, 29.26.

3.2.7 Synthesis of glycoconjugates (8a–e)

To a stirred solution of dimethyl-l-tartrate (0.89 g, 5 mmol) in dichloromethane (30 mL), BF3.Et2O (1.25 mL, 10 mmol) was added under an N2 atmosphere, and the mixture was stirred for 30 min. Each of the glycopyranosyl α-trichloroacetimidates, 7a–e (2.45 g, 5-mmol), was added at 0°C and after 0.5 h, the reaction mixture was allowed to reach an ambient temperature and was then left overnight. The reaction was monitored through TLC, and the crude mixture was concentrated by a rotary evaporator. The crude product was mixed with ethyl acetate (50 mL), successively washed with distilled water and saturated saline (20 mL × 3), and dried over anhydrous magnesium sulfate. The pure product was then obtained by column chromatography (ethyl acetate: n-hexane (3:7)) [51,52].

3.2.8 O(2-3-4-6-Tetra,O-acetyl-β-d-glucopyranosyl)-dimethyl-3-hydroxysuccinate (8a)

Yield: 70%. Colorless oil. [ α ] D 25 = 49.53° (c = 24 mg/2 mL CH2Cl2). (FT-IR): 3,412 (OH), 2,981 (C–H), 1,744 (C–O) 1,337 (CO–C) (Figure S11). 1H-NMR (300-MHz, CDCl3): δ (ppm): 5.4 (d, J = 8.3 Hz, 1-H, H-1), 5.4, 5.4, 4.9 (3-pseudo t, J ∼ 10.2 Hz each, 3-H, H-2, H-3, H-4), 4.7 (d.d, J = 9.6, 2.4 Hz, 1-H, C–H), 4.6 (d, J = 2.4 Hz, 1-H, C–H), 4.5 (d, J = 7.2 Hz, 1-H, O–H), 4.3 (d.d, J = 12.5, 2.5 Hz, 1-H,H-6a), 4.1 (d.d.d, J = 10.4, 3.6, 2.1 Hz, 1-H,H-5), 3.93 (dd, J = 12.5, 2.6 Hz, 1-H,H-6b), 3.8 (s, 3-H, O–CH3), 3.8 (s, 3-H, O–CH3), 2.1, 2.1, 2.1, 2.0 (4s, 12-H, 4 × CH3) (Figure S12). 13C-NMR (75 MHz, CDCl3): δ (ppm): 172.3 (CO–OCH3), 170.6, 169.7, 169.6, 168.1 (4 × CO, acetyl), 96.5 (C-1), 76.6 (C–H), 75.3 (C–H), 72.0, 69.6, 68.9, 68.6 (C-2-C-5), 65.7 (C-6), 53.1 (O–CH3), 52.9 (O–CH3), 20.8, 20.7, 20.6 (2) (4 × CH3, acetyl) (Figure S13). Anal. Calc. for C20H28O15: C, 47.25; H, 5.55; O, 47.20; found: C, 47.21; H, 5.57; O, 47.24.

3.2.9 O(2-3-4-6 Tetra-O-acetyl-β-d-galactopyranosyl) dimethyl-3-hydroxysuccinate (8b)

Yield: 61%. Yellowish color oil. [ α ] D 25 = 24.59° (c = 24 mg/2 mL CH2Cl2). (FT-IR): 3,411 (OH), 2,984 (C–H), 1,746 (CO) 1,330 (CO–C) (Figure S14). 1H-NMR (300 MHz, CDCl3): δ (ppm): 5.4 (d, J = 8.2 Hz, 1-H, H-1), 5.4, 4.9 (2- pseudo t, J ∼ 5.3 Hz each one, 2-H,H-3, H-4), 5.4 (t, J = 11.6 Hz, 1-H, H-2), 4.7 (d.d, J = 9.5, 2.5 Hz, 1-H, C–H),4.6 (d, J = 2.4 Hz, 1-H, C–H),4.5 (d, J = 7.1 Hz, 1-H, O–H), 4.3 (d.d, J = 12.5, 3.6 Hz, 1-H,H-6a), 4.1 (d.d.d, J = 10.4, 3.6, 2.1 Hz, 1-H, H-5), 3.9 (d.d, J = 12.5, 3.6 Hz, 1-H,H-6b), 3.8 (s, 3-H, O–CH3), 3.8 (s, 3-H, O–CH3), 2.1(3), 2.0 (4s, 12-H, 4 × CH3) (Figure S15). 13C-NMR (75 MHz, CDCl3): δ (ppm): 171.6 (COOCH3), 170.1, 169.3, 169.2, 168.1 (4 × CO, acetyl), 96.2 (C-1), 76.3 (CH), 75.1 (CH), 72.1, 69.2, 68.7, 68.5 (C,2-C,5), 65.6 (C,6), 53.2(O–CH3), 52.7 (O–CH3), 20.3, 20.1, 20.0 (2)(CH3, acetyl) (Figure S16). Anal. Calc. for C20H28O15: C, 47.25; H, 5.55; O, 47.20; found: C, 47.23; H, 5.57; O, 47.23.

3.2.10 O (2-3-4-6 TetraO-acetyl-β-d-mannoopyranosyl)-dimethyl-3-hydroxysuccinate (8c)

Yield: 67%. Brown color oil. [ α ] D 25 = 31.51° (c = 24 Mg/2 mL CH2Cl2). (FT-IR): 3,473 (O–H), 2,956 (C–H), 1,736 (C-O), 1,320 (C–O–C) (Figure S17). 1H-NMR (300 MHz, CDCl3): δ (ppm): 5.5 (d, J = 3.7 Hz, 1-H, H,1), 5.4, 5.4 (2-pseudo t, J ∼ 5.2 Hz in each, 2-H,H-2, H, 3), 4.9 (t, J = 12.0 Hz, 1-H, H,4), 4.7 (d.d, J = 9.2, 2.5 Hz, 1-H, C–H), 4.6 (d, J = 2.5 Hz, 1-H, CH),4.59 (d, J = 7.2 Hz, 1-H, O–H), 4.3 (d.d, J = 12.5, 3.6 Hz, 1-H,H-6a), 4.1 (d.d.d, J = 10.3, 3.5, 2.3 Hz, 1-H, H,5), 3.9 (d.d, J = 12.5, 3.6 Hz, 1-H, H,6b), 3.8 (s, 3-H, O–CH3), 3.8 (s, 3-H, O–CH3), 2.2, (2) 2.1(2) (4s, 12-H, 4 × CH3) (Figure S18). 13C-NMR (75 MHz, CDCl3): δ (ppm): 171.7 (COOCH3), 170.3, 169.4, 169.2, 168.5 (4 × CO, acetyl), 95.9 (C-1), 76.2 (CH), 75.1 (CH),72.3, 69.1, 68.6, 68.3 (C-2-C-5), 65.1 (C-6), 53.5 (OCH3), 52.7 (OCH3), 20.2, 20.0, 19.4 (2)(4 × CH3, acetyl) (Figure S19). Anal. Calc. for C20H28O15: C, 47.25; H, 5.55; O, 47.20; found: C, 47.22; H, 5.51; O, 47.16.

3.2.11 O(3-4-6 TriO,acetyl-2-acetamido-β-d-gluco-pyranosyl)-dimethyl-3-hydroxysuccinate (8d)

Yield: 68%. Colorless gel. [ α ] D 25 = 29.41° (c = 24 mg/2 mL CH2Cl2). (FT-IR υ cm−1): 3,421 (O–H), 2,974 (C–H), 1,732 (C-O), 1,310 (CO–C). 1H-NMR (300 MHz, CDCl3): δ (ppm): 6.9 (d, J = 9.5 Hz, 1-H, N–H), 5.6 (d, J = 8.3 Hz, 1-H, H,1), 5.4, 4.9 (2- pseudo t, J ∼ 8.5 Hz in each, 2-H, H,3, H,4), 5.4 (m, 1-H, H,2), 4.7 (d.d, J = 9.3, 2.4 Hz, 1-H, C–H), 4.6 (d, J = 2.4 Hz, 1-H, C–H), 4.5 (d, J = 7.2 Hz, 1-H, O–H), 4.3 (d.d, J = 12.5, 3.6 Hz, 1-H, H,6a), 4.1 (d.d.d, J = 10.4, 3.6, 2.1 Hz, 1-H, H,5), 3.9 (d.d, J = 12.5, 3.6 Hz, 1-H, H,6b), 3.8 (s, 3-H, O–CH3), 3.8 (s, 3-H, O–CH3), 2.1, 2.1(2), 2.07 (4s, 12-H, 4 × CH3). 13C-NMR (75 MHz, CDCl3): δ (ppm): 172.0 (COOCH3), 170.5, 169.3, 169.3, 168.4 (4 × CO, acetyl), 96.0 (C-1), 76.2 (CH), 75.3 (CH), 72.2, 69.1, 68.6, 68.2 (C-2-C-5), 64.6 (C-6), 53.4 (OCH3), 52.3 (OCH3), 20.4, 20.2, 20.1 (2) (4 × CH3, acetyl). Anal. Calc. for C20H29NO14: C, 47.34; H, 5.76; N, 2.76; O, 44.14; found: C, 47.30; H, 5.73; N, 2.74; O, 44.11.

3.2.12 O(3-4-6-TriO-acetyl-2-acetamido-β,d-galactopyranosyl)-dimethyl-3-hydroxysuccinate (8e)

Yield: 59%. Yellowish gel type. [ α ] D 25 = 22.51° (c = 24 mg/2 mL CH2Cl2). (FT-IR): 3,423 (OH), 2,984 (C–H), 1,735 (C-O), 1,313 (CO–C). 1H-NMR (300 MHz, CDCl3): δ (ppm): 6.9 (d, J = 9.2 Hz, 1-H, N–H), 5.6 (d, J = 8.3 Hz, 1-H, H,1), 5.4, 4.9 (2-pseudo t, J ∼ 4.8 Hz each one, 2-H,H,3, H,4), 5.4 (m, 1-H, H,2), 4.7 (d.d, J = 9.3, 2.5 Hz, 1-H, C–H), 4.6 (d, J = 2.5 Hz, 1-H, C–H), 4.5 (d, J = 7.3 Hz, 1-H, O–H), 4.3 (d.d, J = 12.5, 3.6 Hz, 1-H,H,6a), 4.1 (d.d.d, J = 10.4, 3.6, 2.1 Hz, 1-H,H,5), 3.9 (d.d, J = 12.5, 3.6 Hz, 1-H,H,6b), 3.8 (s, 3-H, O–CH3), 3.8 (s, 3-H, O–CH3), 2.1(2), 2.0 (2)(4s, 12-H, 4 × CH3). 13C-NMR (75 MHz, CDCl3): δ (ppm): 171.5 (CO–OCH3), 170.3, 169.1, 169.0, 168.5 (4 × CO, acetyl), 96.4 (C-1), 76.2 (CH), 75.5 (CH), 72.1, 69.2, 68.2, 68.1 (C,2-C,5), 64.7 (C,6), 53.5 (OCH3), 52.7 (OCH3), 20.5, 20.3, 20.1 (2) (4 × CH3, acetyl). Anal. Calc. for C20H29NO14: C, 47.34; H, 5.76; N, 2.76; O, 44.14; found: C, 47.36; H, 5.70; N, 2.72; O, 44.17.

3.3 Antimicrobial assays

Antimicrobial resistance (AMR) occurs when microorganisms such as bacteria, fungi, parasites, and viruses get accustomed and multiply in the presence of drugs that were once used to inhibit them [53,54]. AMR is regarded as a prominent risk to community health systems all over the world. Despite numerous actions taken in recent years to solve this issue, the trends of global AMR reveal no signs of decline. AMR is attributed to the misuse and overuse of antimicrobial agents in the healthcare systems and the agricultural sector. Furthermore, the instinctual evolution, alteration in the DNA sequence of bacterial cells, and transfer of the resistant genes via horizontal gene transmission are substantial factors in AMR. Considering the serious threat of AMR and also to validate the docking studies of our target compounds, their antimicrobial assays against the selected strains of bacteria, fungi, and leishmania were performed.

The antibacterial potential of the synthesized compounds was evaluated against selected bacterial strains. The results are summarized in Table 1. In the present study, three concentrations (1,000, 500, and 250 μg/mL) of the selected compounds (8a–e) were employed to study the inhibition potential against five bacterial strains: E. coli, S. aureus, S. typhi, A. marina, and P. aeruginosa. All five novel glycoconjugates (8a–e) were tested for their in vitro antibacterial effect versus different strains of bacteria. All the compounds showed good to excellent activity against E. coli, S. aureus, S. typhi, A. marina, and P. aeruginosa. Compound 8a showed a 16-, 15- and 17-mm zone of inhibition versus E. coli, S. aureus, and S. typhi at 1,000 μg/mL. However, there was a decline in the activity at 500 and 250 μg/mL, respectively, in all the series. Compound 8b showed 17, 18 and 9 mm zones of inhibition versus E. coli, S. aureus, and S. typhi at 1,000 μg/mL. Compounds 8d and 8e were found to be the most active among the series, which showed 22, 19, and 24 mm and 25, 17, and 22 mm inhibition zones for E. coli, S. aureus, and S. typhi at 1,000 μg/mL.

Table 1

Antibacterial activities at three different concentrations against E. coli, S. aureus, S. typhi, A. marina, and P. aeruginosa

Zone of inhibition (mm)
S. No. Codes E. coli S. aureus S. typhi A. marina P. aeruginosa
Conc. (μg/mL) Conc. (μg/mL) Conc. (μg/mL) Conc. (μg/mL) Conc. (μg/mL)
1,000 500 250 1,000 500 250 1,000 500 250 1,000 500 250 1,000 500 250
1 8a 16 11 04 15 08 07 17 11 08 15 11 09 19 11 08
2 8b 17 11 06 18 15 11 09 04 05 18 11 09 12 09 08
3 8c 13 15 09 17 11 08 16 14 13 16 08 08 12 13 11
4 8d 22 13 10 19 12 07 24 18 12 19 14 12 16 11 08
5 8e 25 16 09 17 18 12 22 15 13 20 14 13 18 14 11
6 Chloramphenicol 38 35 23 38 33 26 35 24 22 38 35 25 38 33 26

Zone of inhibition diameter in mm. (Activity): above 18 mm (significant activity), 16–18 mm (good activity) 13–15 mm (low activity), 9–12 mm (non-significant), <9 mm (no activity).

Compounds (8a–e) showed good activity against A. marina and P. aeruginosa. Compound 8a showed a 15 and 19 mm zone of inhibition against A. marina and P. aeruginosa at 1,000 μg/mL. A decline in the activity was observed at 500 and 250 μg/mL, respectively, in all the series. Compound 8b showed an 18 and 12 mm zone of inhibition at 1,000 μg/mL, while 8d and 8e were found to be most active among the series as compared to the standard drug chloramphenicol, which showed 19, 16 mm and 20 and 18 mm zones of inhibition for A. marina and P. aeruginosa at 1,000 μg/mL.

3.4 Antifungal bioassay

Table 2 summarizes the antifungal activities of the synthesized compounds. Among the glycoconjugates, compound 8a showed a 17 and 20% zone of inhibition against C. albicans and A. flavus at 500 µg/mL, and compound 8b with 13 and 16% zone of inhibition. Compound 8c showed a 19 and 15% zone of inhibition against C. albicans and A. flavus. Compounds 8d and 8e showed 23, 18, 18, and 19% zones of inhibition, respectively, against C. albicans and A. flavus at 500 µg/mL concentration. However, at 250 μg/mL concentration, there was a decrease in the inhibition potential of all the compounds. Compounds 8d and 8e were found to be more effective with reference to the standard drug.

Table 2

Antifungal activities at three different concentrations against C. albicans and A. flavus

S. No. Code C. albicans A. flavus
500 μg/mL 250 μg/mL 100 μg/mL 500 μg/mL 250 μg/mL 100 μg/mL
1 8a 17 11 9 20 18 13
2 8b 13 8 9 16 7 8
3 8c 19 14 6 15 9 5
4 8d 23 14 11 18 12 9
5 8e 18 14 11 19 16 8
6 Fluconazole 32 28 20 32 28 20

Zone of inhibition diameter in mm. (Activity): above 18 mm (significant activity), 16–18 mm (good activity), 13–15 mm (low activity), 9–12 mm (non-significant), <9 mm (no activity).

3.5 Antileishmanial bioassay

All the synthesized glycoconjugates (8a–e) were evaluated for their antileishmanial activity using Leishmania tropica promastigotes for in vitro investigation. The results are shown in Table 3. Among the synthesized glycoconjugates, compounds (8a), (8b), and (8d) displayed good activity, whereas compounds (8c) and (8e) showed low activity.

Table 3

% Inhibition of glycoconjugates (8a–e) versus L. tropica leishmania

S. No. Sample codes IC50 (μg/mL ± S.D)*
1 8a 0.65 ± 0.01
2 8b 0.68 ± 0.09
3 8c 0.81 ± 0.16
4 8d 0.61 ± 0.27
5 8e 0.79 ± 0.11
6 Amphotericin B 0.56 ± 0.20

*Criteria for IC-50 non-significant activity (0.99), low activity (0.80–0.95), moderate activity (0.70–0.79), good activity (0.60–0.69), and significant activity (<0.56–0.59).

3.5.1 Docking results of A. flavus

The results of molecular docking interactions of compounds (8a–e) with A. flavus (PDB ID. 7PUF) are shown in Figure 2 [55]. Compound 8a formed three hydrogen bond interactions with residues Arg108, Glu31, and Arg128, and the binding energy was −12.23 kJ/mol. Compound 8b formed two hydrogen bonds with residues Arg108 and Arg128, and the binding energy was −09.38 kcal/mol. Compound 8c formed five interactions, including two hydrogen bonding with residues Arg108 and Arg 128 and three carbon–hydrogen bonds with residues Trp106, Glu31, and His104, whereas the binding energy was found to be −13.34 kcal/mol. Compound 8d formed two hydrogen bonding interactions with residue Arg128 and one carbon–hydrogen bond with residue Glu31. The binding energy was −08.77 kcal/mol. Compound 8e formed only two interactions: one hydrogen bond with residue Arg128 and one carbon–hydrogen bond with residue Pro76. The binding energy was −07.78 kcal/mol [56].

Figure 2 2D and 3D molecular docking interactions of compound (8a–e) with A. flavus (7PUF).
Figure 2

2D and 3D molecular docking interactions of compound (8a–e) with A. flavus (7PUF).

3.5.2 Docking study of compounds (8a–e) against S. typhi (6p4s)

The docking results of compounds (8a–e) against S. typhi 6p4s are shown in Figure 3. Compound 8a established four interactions comprising three conventional hydrogen bonds with residues Leu125, Thr26, and Trp25, one carbon–hydrogen bond with residue Glu84, and one nonconventional donor–donor interaction. The binding energy was −13.23 kcal/mol. Compound 8b formed five total interactions, including three conventional hydrogen bonds with residues Leu125, Thr26, and Trp25, one carbon–hydrogen bond with Glu84, and one unfavorable donor–donor interaction with residue Ser126. The binding energy was −14.45 kcal/mol. Compound 8c established six interactions, including four conventional hydrogen bonding interactions with residues Asn115, 120, 106, and Val68 and two carbon–hydrogen bonds with residues Phe117 and Ser118. The binding energy was calculated to be −14.56 kcal/mol. Compound 8d formed six interactions as well, including three conventional hydrogen bonds with residues Trp25, Thr26, and Ser126 and two carbon–hydrogen bonds with species Pro135 and Gly136. The last interaction was an unfavorable acceptor–acceptor interaction with residue Ser81. The calculated binding energy was −12.78 kcal/mol. Compound 8e formed five interactions, including three conventional hydrogen bonds with residues Lys105, Ala119, and Asn120, one carbon–hydrogen bond with residue Phe117, and one unfavorable acceptor–acceptor interaction with residue Thr34. The binding energy was −12.87 kcal/mol [57].

Figure 3 2D and 3D molecular docking interactions of compounds (8a–e) with S. typhi (6p4s).
Figure 3

2D and 3D molecular docking interactions of compounds (8a–e) with S. typhi (6p4s).

3.5.3 Docking study against C. albicans

The results of molecular docking interactions of compounds (8a–e) with C. albicans (PDB ID.5FSA) are shown in Figure 4 [57].

Figure 4 2D and 3D molecular docking interactions of compounds (8a–e) with C. albicans (5fsa).
Figure 4

2D and 3D molecular docking interactions of compounds (8a–e) with C. albicans (5fsa).

Compound 8a established five interactions, including three conventional hydrogen bonding interactions with residues His468 and Arg381, whereas two carbon–hydrogen bonds with residues Gly307 and Lys143. The binding energy was −09.87 kcal/mol. Compound 8b formed a total of seven interactions, including three carbon–hydrogen bonds with residues Asn435 and Ile471 and five were hydrogen bonding interactions with residues Ser453, Lys451, and Lys147. The binding energy was −14.77 kcal/mol. Compound 8c formed nine interactions comprising three carbon–hydrogen bonds with residues Gly465, Leu150, and Ile471and six hydrogen bonding interactions with residues Ser436, Ser453, Arg469, Lys147, and Gln474. The binding energy was −15.789 kcal/mol. Compound 8d formed nine interactions which included two carbon–hydrogen bonds with residues Gln474 and Ile471 and seven hydrogen bonding interactions with residues Ser436, Ser453, Arg469, Lys147, and Lys451. The calculated binding energy was −13.23 kcal/mol. Compound 8e formed two interactions: one hydrogen bonding with residue Tyr132 and one carbon–hydrogen bonding with residue Gly307. The calculated binding energy was −07.989 kcal/mol [57].

3.5.4 Docking study against A. marina

The molecular docking interactions of compounds (8a–e) with protein (PDB ID. 7COY) are shown in Figure 5 [58]. Compound 8a formed four interactions, and all were hydrogen bonds with residues Tyr146, Asn104, Asp257, and Arg182. The calculated binding energy was −10.567 kcal/mol. Compound 8b established six interactions with protein, and all were hydrogen bonds with residues Tyr146, Asn104, Asp257, Arg182, and Ser254; the binding energy was −06.965 kcal/mol. Compound 8c formed five hydrogen bonding interactions with residues Tyr146, Asn104, Asp257, Arg182, and Ser254. The calculated binding energy was −10,345 kcal/mol. A total of nine interactions were expressed by compound 8d, including seven hydrogen bonds with residues Arg226, Asp229, Gly118, and Trp79. One pi–sigma interaction with residue Trp198 and one carbon–hydrogen bond with residue Asn228. The calculated binding energy was −12.675 kcal/mol. Compound 8e formed five interactions with residues Tyr146, Asn104, Asp257, Arg182, and Ser254, and the binding energy was −11.963 kcal/mol [59].

Figure 5 2D and 3D molecular docking interactions of compounds (8a–e) with A. marina (7coy).
Figure 5

2D and 3D molecular docking interactions of compounds (8a–e) with A. marina (7coy).

3.5.5 Docking study against P. aeruginosa (4cl6)

The molecular docking interactions of compounds (8a–e) are shown in Figure 6. Compound 8a formed four interactions: two hydrogen bonds with residues Ala105 and Gly103, and one carbon–hydrogen bond with residue Gln88, and one unfavorable acceptor–interaction with residue Gln27. The calculated binding energy was −06.798 kcal/mol. Compound 8b formed a total of five interactions: two hydrogen bonds with residues Arg104 and Ala105, and three interactions were carbon–hydrogen bondings with residues Gly103, Gly91, and Gln88. The binding energy was −07.90 kcal/mol. Compound 8c formed four hydrogen bonding interactions with residues Ala105, Gly103, Phe92, and Gln27. The binding energy was −09.234 kcal/mol. Compound 8d established three hydrogen bonding interactions with residues Ala105, Arg104, and Ala105. The compound formed one carbon–hydrogen interaction with residue Ala105. An unfavorable acceptor interaction of compound 8d with residue TRP87 was also observed. The binding energy value was noted to be −08.252 kcal/mol. A total of seven interactions for compound 8e with 4cl6 were noted. It formed four hydrogen bonds with residues Ala105, Gln88, Gln27, and Arg104. Three carbon–hydrogen interactions with residues Asp84, Gly91, and Gly103 were observed. The binding energy value was calculated to be −09.468 kcal/mol [60].

Figure 6 2D and 3D molecular docking interactions of compounds (8a–e) with P. aeruginosa (4cl6).
Figure 6

2D and 3D molecular docking interactions of compounds (8a–e) with P. aeruginosa (4cl6).

3.5.6 Docking study against S. aureus

The molecular docking interactions of compounds (8a–e) with S. aureus (PDB ID 3FYV) are shown in Figure 7 [61].

Figure 7 2D and 3D molecular docking interactions of compounds (8a–e) with S. aureus (3fyv).
Figure 7

2D and 3D molecular docking interactions of compounds (8a–e) with S. aureus (3fyv).

Compound 8a formed six interactions, including two hydrogen bondings with residues Thr46 and Leu20 and four carbon–hydrogen bonds with residues Phe92, Thr121, Gly21, and Ser49. The calculated binding energy was −08.433 kcal/mol. Compound 8b formed five interactions: two hydrogen bonds with residues Leu20 and Ala7 and three carbon hydrogen with residues Ser49, Ala18, and Phe92. The calculated binding energy was −06.766 kcal/mol. Compound 8c established six interactions consisting of two hydrogen bonds with residues Thr46 and Leu20 and four carbon–hydrogen bonds with residues Ser49, Gly15, Gly94, and Phe92. The binding energy was −09.765 kcal/mol. Compounds 8d and 8e formed six interactions: three hydrogen bonds with residues Thr46, Leu20, and Phe92 and three carbon–hydrogen bonds with residues Ser49, Gly15, and Asn18. The calculated binding energies were −10.234 and −10.654 kcal/mol [61].

3.5.7 Docking study against E. coli

The molecular docking interactions of compounds (8a–e) with E. coli (pdb id. 1kzn) are shown in Figure 8 [62].

Figure 8 2D and 3D molecular docking interactions of compounds (8a–e) with E. coli (1kzn).
Figure 8

2D and 3D molecular docking interactions of compounds (8a–e) with E. coli (1kzn).

Compound 8a formed five interactions, including four with hydrogen bondings with residue Asn46 and one carbon–hydrogen bond with residue Gly77. The calculated binding energy was −05.987 kcal/mol. Compound 8b formed a total of seven hydrogen bonding interactions with residues Asn46, Val20, Arg76, and Ser121. The binding energy was −11.873 kcal/mol. Compound 8c formed three hydrogen bonds with residues Ser121, Val20, and Asn46. The binding energy was −04.332 kcal/mol. A total of six interactions were formed by compound 8d, including five hydrogen bonds with residues Asp207, Arg209, Tyr184, and Lys212 and one carbon–hydrogen bond with residue Glu181. The calculated binding energy was −17.657 kcal/mol. Compound 8e formed five interactions: three hydrogen bonds with residues Ala96, Asn46, and Val120 and two carbon–hydrogen bonds with residues Gly119 and Ile90. The binding energy was−07.543 kcal/mol [52].

4 Conclusions

Novel glycoconjugates 8a–e were synthesized from glycolpyranosyl α-trichloroacetimidates (sugar-OTCA) as glycosyl donors and dimethyl L-tartrate as an aglycone acceptor. They were fully characterized by spectro-analytical techniques and were tested for their in vitro antibacterial and fungal effects versus distinct strains of bacteria and fungi. The synthesized glycoconjugates also exhibited promising antileishmanial activity against Leishmania tropica. All the compounds exhibited good to excellent activity versus E. coli, S. aureus, S. typhi, A. marina, and P. aeruginosa. All compounds 8a–e exhibited good to significant inhibition potential against fungal strains (C. albicans and A. flavus). The preliminary experimental data were also supported by the in silico docking analysis of the synthesized compounds with the selected bacterial and fungal strains. All the compounds expressed encouraging results like maximum interactions and acceptable values of binding energies. The in vitro and in silico results were in agreement. The synthesized compounds may prove to be useful drug candidates against bacterial and fungal infections in the future.

Acknowledgments

The authors extend their appreciation to the researchers supporting Project number (RSP2024R110) King Saud University, Riyadh, Saudi Arabia, for financial support.

  1. Funding information: The authors extend their appreciation to the researchers supporting Project number (RSP2024R110), King Saud University, Riyadh, Saudi Arabia, for financial support.

  2. Author contributions: S.W.K.: conceptualization, methodology, and experimentation; S.N.: data curation and methodology; M.Z.: writing-original draft; M.N.U.: software and validation; A.I:; data curation; M.K.: formal analysis and investigation; N.A.: software and validation; H.U.R.: data curation; N.G.: formal analysis, writing-review, and editing; R.U. and E.A.: funding and technical assistance.

  3. Conflict of interest: All the authors declare hereby that they have no conflict of interest.

  4. Ethical approval: The conducted research is not related to either human or animals use.

  5. Data availability statement: All data generated or analysed during this study are included in this published article [and its supplementary information files].

References

[1] Varki A, Cummings RD, Esko JD. Essentials of Glycobiology. NY: Cold Spring Harbor Press; 2017.Search in Google Scholar

[2] (a) Kuberan B, Linhardt RJ. Carbohydrate based vaccines. Curr Org Chem. 2000;4:653–77. (b) Hütter J, Lepenies B. In: Lepenies B, editor. Carbohydrate-based vaccines: Methods and protocols. New York, NY: Springer New York; 2015. p. 1–10.Search in Google Scholar

[3] Avci FY, Kasper DL. How bacterial carbohydrates influence the adaptive immune system. Annu Rev Immunol. 2010;28:107–30 [PubMed: 19968562].10.1146/annurev-immunol-030409-101159Search in Google Scholar PubMed

[4] Avery OT, Goebel WF. Chemo-immunological studies on conjugated carbohydrate-proteins: V. The immunological specifity of an antigen prepared by combining the capsular polysaccharide of type III pneumococcus with foreign protein. J Exp Med. 1931;54:437–47.10.1084/jem.54.3.437Search in Google Scholar PubMed PubMed Central

[5] Astronomo RD, Burton DR. Carbohydrate vaccines: Developing sweet solutions to sticky situations? Nat Rev Drug Discov. 2010;9:308–24.10.1038/nrd3012Search in Google Scholar PubMed PubMed Central

[6] Pritchett TJ, Brossmer R, Rose U, Paulson JC. Recognition of monovalent sialosides by influenza virus H3 hemagglutinin. Virology. 1987;100:502–6.10.1016/0042-6822(87)90026-2Search in Google Scholar PubMed

[7] Gruters RA, Neefjes JJ, Tersmette M, Tulp A, Huisman G. Interference with HIV-induced syncytium formation and viral infectivity by inhibitors of trimming glucosidase. Nature. 1987;330:74–7.10.1038/330074a0Search in Google Scholar PubMed

[8] Bock K, Breimer ME, Brignole A, Hasson GC, Karlsson KA, Larson G. Specificity of binding of a strain of uropathogenic Escherichia coli to Gal alpha 1-4-Gal-containing glycosphingolipids. J Biol Chem. 1985;260:8545–55.10.1016/S0021-9258(17)39507-8Search in Google Scholar

[9] Krivan HC, Roberts DD, Ginsburg V. Many pulmonary pathogenic bacteria bind specifically to the carbohydrate sequence GalNAcbeta 1-4-Gal found in some glycolipids. Proc Natl Acad Sci. 1988;85:6157–64.10.1073/pnas.85.16.6157Search in Google Scholar PubMed PubMed Central

[10] Karlsson KA. Differentiation between transmembrane helices and peripheral helices by the deconvolution of circular dichroism spectra of membrane proteins. Ann Rev Bio Chem. 1989;59:309–328.10.1146/annurev.bi.58.070189.001521Search in Google Scholar PubMed

[11] Thieme J, Sauerbrei B. Chemoenzymatische synthesen via sialyl oligosacchariden mitimmobilisiertersialidase. Angew Chem. 1991;103:1521–3. Angew Chem Int Ed Engl. 1991;30:1503–5.10.1002/anie.199115031Search in Google Scholar

[12] Nilsson KG. In: Khan SH, O’Neil RA, editors. Modern Methods in Carbohydrate Synthesis. Harwood Academic Publisher; 1996.Search in Google Scholar

[13] Beyer TA, Sadler JE, Rearick JI, Paulson JC. Glycosyltransferases and their use in assessing oligosaccharide structure and structure-function relationships. Adv Enzymol. 1981;52:23–175.10.1002/9780470122976.ch2Search in Google Scholar PubMed

[14] Wong CH. Practical synthesis of oligosaccharides based on glycosyltransferases and glycosylphosphites. In: Khan SH, Neil RA, editors. Modern Methods in Carbohydrate Synthesis. Amsterdam, The Netherlands: Harwood Academic Publishers; 1996. p. 467–91.10.1201/9781003077329-19Search in Google Scholar

[15] Koenigs W, Knorr E. Koenig-Knorr glycosidation. Chem Ber. 1901;34:957–81.10.1002/cber.190103401162Search in Google Scholar

[16] Wulff G, Rohle G. Results and problem of O-glycosides. Angew Chem. 1974;86:173–87. Angew Chem Int Ed Engl, 1974;13:157–174.10.1002/anie.197401571Search in Google Scholar PubMed

[17] Mukayama T, Murai Y, Shoda S. An efficient method for glucosylation of hydroxyl compounds using glucopyranosyl fluoride. Chem Lett. 1981;10:431–2.10.1246/cl.1981.431Search in Google Scholar

[18] Randall JL, Nicolau KC. Taylor NF. In Fluorinate carbohydrates: chemical and biological aspects. Washington: A. Chem. Soc.; 1988.Search in Google Scholar

[19] Paulsen H. Fortschritte bei der selektiven chemischen Synthese komplexer Oligosaccharide. Angew Chem. 1982;94:184–201. Angew Chem Int Ed Engl. 1982;21:155–82.10.1002/ange.19820940304Search in Google Scholar

[20] Schmidt RR, Michel J. Einfache Synthese von α-und β-O-Glykosylimidaten; Herstellung von Glykosiden und Disacchariden. Angew Chem. 1980;92:763–4. Angew Chem Int Ed Engl. 1980;19:731–2.10.1002/ange.19800920933Search in Google Scholar

[21] Stauch T. Novel trichloroacetimidates and their reactions. Ph.D. thesis. University of Konstanz; 1995.Search in Google Scholar

[22] Douglas SP, Whitfield DM, Krepinsky J. Silver trifluoromethanesulfonate (triflate) activation of trichloroacetimidates in glycosylation reactions. J Carbohydr Chem. 1993;12:131–6.10.1080/07328309308018547Search in Google Scholar

[23] Schmidt RR, Michel J. Glycosyl imidate, direct synthesis of O-α-and O-β-glycosylimidates. Liebigs Ann Chem. 1984;1984:1343–57.10.1002/jlac.198419840710Search in Google Scholar

[24] Urban FJ, Moore BS, Breitenbach R. Synthesis of trigogenyl-β-O-cellobioside heptaacetate and glycoside tetraacetate via Schmidt’s trichloroacetimidate method; some new observations. Tetrahedron Lett. 1990;31:4421–4.10.1016/S0040-4039(00)97637-8Search in Google Scholar

[25] Patil VJ. A simple access to trichloroacetimidates. Tetrahedron Lett. 1996;37:1481–4.10.1016/0040-4039(96)00044-5Search in Google Scholar

[26] Schmidt RR, Jung KH. Trichloroacetimidates in carbohydrates chemistry and biology, part I: Chemistry of saccharides. Vol 1. Weinheim: Wiley-VCH; 2000. p. 5–59.Search in Google Scholar

[27] Nef JU. About the zweiwerthige carbon atom. The chemistry of cyanogen and isocyans. Liebigs Ann Chem. 1895;287:265–359.Search in Google Scholar

[28] Lubineau A, Carpentier KB, Auge C. Porcine liver (2 → 3)-α-sialyltransferase: substrate specificity studies and application of the immobilized enzyme to the synthesis of various sialylated oligosaccharide sequences. Carbohydr Res. 1997;300:161–7.10.1016/S0008-6215(97)00043-8Search in Google Scholar PubMed

[29] Mayer TG, Schmidt RR. Glycosylimidates. An efficient synthesis of galactinol and isogalacatinol. Liebigs Ann/Recl. 1997;1997:859–63.10.1002/jlac.199719970511Search in Google Scholar

[30] Ishida H, Ando H, Ito H, Ishida H, Kiso M, Hasegawa A. Synthetic studies on sialo glycoconjugates 91: Total synthesis of gangliosides GD1C and GT1A. J Carbohydr Chem. 1997;16:413–328.10.1080/07328309708007325Search in Google Scholar

[31] Kinzy W, Schmidt RR. Application of the trichloroacetimidate method to the synthesis of glycopeptides of the mucin type containing a β-d-Galp-(1 → 3)-d-GalpNAcunit. Carbohydr Res. 1987;164:265–76.10.1016/0008-6215(87)80135-0Search in Google Scholar PubMed

[32] Depew KM, Zeman SM, Boyer SH, Denhart DJ, Ikemoto N, Danishefsky SJ, et al. Synthesis and a preliminary DNA binding study of hybrids of the carbohydrate domain of calicheamicin γ and the aglycone of daunorubicin: Calichearubicins A and B. Angew Chem Int Ed Engl. 1997;35:2797–801.10.1002/anie.199627971Search in Google Scholar

[33] Olson SH, Danishefsky S. Reductive desilanolation as a route to benzonitriles. An application to a concise synthesis of the aromatic sector of calicheamicin. Tetrahedron Lett. 1994;35:7901–4.10.1016/0040-4039(94)80006-5Search in Google Scholar

[34] Rashid H, Khan SW, Khan M, Nadhm A, Rehman N, Tariq M, et al. Synthesis, Characterization, X-Ray crystallography and antileishmanial activities of N-linked and O-linked glycopyranosides from L-tartaric acid. Journal of chemistry. 2018;2018:1–9.10.1155/2018/9648710Search in Google Scholar

[35] Khan SW, Zaidi JH, Khan GS, Rashid H, Umar MN, Jan AK, et al. Synthesis and characterization of monoaryl esters of L‑tartaric acid and their process for fries’ rearrangement. J Iran Chem Socy. 2015;12:1819–27.10.1007/s13738-015-0657-1Search in Google Scholar

[36] Scriven EFV. 4-dialkylaminopyridines: super acylation and alkylation catalysts. Chem Soc Rev. 1983;12:129–61.10.1039/cs9831200129Search in Google Scholar

[37] Hudson CS, Dale JK. A comparison of the optical rotatory powers of the alpha and beta forms of certain acetylated derivatives of glucose. J Am Chem Soc. 1915;37:1264–70.10.1021/ja02170a025Search in Google Scholar

[38] Yu B, Xie J, Deng S, Hui Y. First synthesis of a bi-desmosidic triterpene saponin by a highly efficient procedure. J Am Chem Soc. 1999;121:12196–7.10.1021/ja9926818Search in Google Scholar

[39] Ren T, Liue D. Synthesis of targetable cationic amphiphiles. Tetrahedron lett. 1999;40:7621–5.10.1016/S0040-4039(99)01558-0Search in Google Scholar

[40] (a) Schmidt RR. New methods for the synthesis of glycosides and oligosaccharides—are there alternatives to the Koenigs‐Knorr method? [New synthetic methods (56)]. Angew Chem Int Ed Engl. 1986;25:212–35. (b) Excoffier G, Gagnaire D, Utille JP. Coupure sélective par l’hydrazine des groupements acétyles anomères de résidus glycosyles acétylés. Carbohydr Res. 1975;39:368–73.Search in Google Scholar

[41] Washington JAH, Sutter VL. Lennette EH, Balows A, Hausler WJ, Truant JP, editors. Manual of clinical microbiology, 3rd edn. Washington, DC: American Society for Microbiology; 1980. p. 453–8.Search in Google Scholar

[42] Koneman E. Diagnostic microbiology Vogel’s textbook of practical organic chemistry, 4th edn. Beccles and London: ELBS Edition, William Clowes Limited; 1996. p. 1131.Search in Google Scholar

[43] Zhai L, Chen M, Blom J, Theander TG, Christensen SB, Kharazmi A. The antileishmanial activity of novel oxygenated chalcones and their mechanism of action. J Antimicro Chemother. 1999;43:793–803.10.1093/jac/43.6.793Search in Google Scholar PubMed

[44] Trott O, Olson AJ. Auto Dock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010;31:455–61.10.1002/jcc.21334Search in Google Scholar PubMed PubMed Central

[45] Schmidt RR, Jung K-H. In: Ernst B, Hart GW, Sinay P, editors. Trichloroacetimidates in carbohydrates chemistry ang biology, part I: Chemistry of saccharides. Vol 1. Weinheim: Wiley-VCH; 2000. p. 5–59.10.1002/9783527618255.ch2Search in Google Scholar

[46] Nef JU. Ueber das zweiwerthige Kohlenstoffatom. Die Chemie des Cyans und des Isocyans. Liebigs Ann Chem. 1895;287:265–359.10.1002/jlac.18952870303Search in Google Scholar

[47] (a) Schmidt RR. In: Hasegawa A, Ogura M, Suami T, editors. carbohydrates-synthetic methods and application in medicinal chemistry. Tokyo: Kodanasha Scientific; 1992. (b) Schmidt RR, Michel J. O-(α-D-Glucopyranosyl) richloroacetimidate as a Glucosyl Donor. J Carbohydr Chem. 1985;25:141–69.Search in Google Scholar

[48] (a) Schmidt RR, Rücker E. Stereoselective glycosidations of uronic acids. Tetrahedron Lett. 1980;21:1421–4. (b) Toepfer A, Schmidt RR. Muramic acid derivatives as glycosyl donors for the synthesis of muramyl-containing glycosphingolipids and fatty acids. Carbohydr Res. 1990;202:193–205.Search in Google Scholar

[49] (a) Schmidt RR. Recent developments in the synthesis of glycoconjugates. Pure Appl Chem. 1989;61:1257–70. (b) Schmidt RR. In: Trost BM, Fleming I, Winterfeldt E, editors. Comprehensive organic synthesis. Vol. 6. Oxford: Pergamon Press; 1991.Search in Google Scholar

[50] Schmidt RR, Kinzy W. Advances in Carbohydrate Chemistry and Biochemistry. Adv Cabohydr Chem Biochem. 1994;50:21–123.10.1016/S0065-2318(08)60150-XSearch in Google Scholar

[51] Cheng H, Cao X, Xian M, Fang L, Cai TB, Ji JJ, et al. Synthesis and enzyme-specific activation of carbohydrate-geldanamycin conjugates with potent anticancer activity. J Med Chem. 2005;48:645–52.10.1021/jm049693aSearch in Google Scholar PubMed

[52] Founou RC, Founou LL, Essack SY. Clinical and economic impact of antibiotic resistance in developing countries: a systematic review and meta-analysis. PloS One. 2017;12:e0189621. 10.1371/journal.pone.018962129267306 Search in Google Scholar

[53] Antibiotic resistance: a global threat features CDC. https://www.cdc.gov/features/antibiotic-resistance-global/index.html, Accessed 915, 2019.Search in Google Scholar

[54] Porooshat D. Antimicrobial Resistance: Implications and Costs. Infection and Drug Resistance. 2019;12:3903–10. 10.2147/IDR.S234610 Search in Google Scholar PubMed PubMed Central

[55] Prange T, Carpentier P, Dhaussy AC, Girard E, Colloc’h N. Comparative study of the effects of high hydrostatic pressure per se and high argon pressure on urate oxidase ligand stabilization. Acta Cryst D. 2022;78:162–73.10.1107/S2059798321012134Search in Google Scholar PubMed

[56] Lee S, Yang YA, Milano SK, Nguyen T, Ahn C, Sim JH, et al. Salmonella Typhoid Toxin PltB Subunit and Its Non-typhoidal Salmonella Ortholog Confer Differential Host Adaptation and Virulence. Cell Host Microbe. 2020;27:937–49.e6.10.1016/j.chom.2020.04.005Search in Google Scholar PubMed PubMed Central

[57] Hargrove TY, Friggeri L, Wawrzak Z, Qi A, Hoekstra WJ, Schotzinger RJ, et al. Structural analyses of Candida albicans sterol 14 alpha-demethylase complexed with azole drugs address the molecular basis of azole-mediated inhibition of fungal sterol biosynthesis. J Biol Chem. 2017;292:6728–43.10.1074/jbc.M117.778308Search in Google Scholar PubMed PubMed Central

[58] Hamaguchi T, Kawakami K, Shinzawa-Itoh K, Inoue-Kashino N, Itoh S, Ifuku K, et al. Structure of the far-red light utilizing photosystem I of Acaryochloris marina. Nat Commun. 2021;12:2333.10.1038/s41467-021-22502-8Search in Google Scholar PubMed PubMed Central

[59] Kawakami K, Yonekura K, Hamaguchi T, Kashino Y, Shinzawa-Itoh K, Inoue-Kashino N, et al. Structure of the far-red light utilizing photosystem I of Acaryochlorismarina. Nat Commun. 2021;12:2333.10.2210/pdb7coy/pdbSearch in Google Scholar

[60] Moynie L, Hope AG, Finzel K, Schmidberger J, Leckie SM, Schneider G, et al. A Substrate mimic allows high throughput assay of the faba protein and consequently the identification of a novel inhibitor of pseudomonas aeruginosa. J Mol Biol. 2016;428:108–20.10.1016/j.jmb.2015.10.027Search in Google Scholar PubMed PubMed Central

[61] Oefner C, Parisi S, Schulz H, Lociuro S, Dale GE. Inhibitory properties and X-ray crystallographic study of the binding of AR-101, AR-102 and iclaprim in ternary complexes with NADPH and dihydrofolate reductase from Staphylococcus aureus. Acta Crystallogr D Biol Crystallogr. 2009;65:751–7.10.1107/S0907444909013936Search in Google Scholar PubMed

[62] Lafitte D, Lamour V, Tsvetkov PO, Makarov AA, Klich M, Deprez P, et al. DNA gyrase interaction with coumarin-based inhibitors: the role of the hydroxybenzoate isopentenyl moiety and the 5’-methyl group of the noviose. Biochemistry. 2002;41:7217–23.10.1021/bi0159837Search in Google Scholar PubMed

Received: 2023-11-11
Revised: 2023-12-20
Accepted: 2024-01-12
Published Online: 2024-02-13

© 2024 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

Articles in the same Issue

  1. Regular Articles
  2. Porous silicon nanostructures: Synthesis, characterization, and their antifungal activity
  3. Biochar from de-oiled Chlorella vulgaris and its adsorption on antibiotics
  4. Phytochemicals profiling, in vitro and in vivo antidiabetic activity, and in silico studies on Ajuga iva (L.) Schreb.: A comprehensive approach
  5. Synthesis, characterization, in silico and in vitro studies of novel glycoconjugates as potential antibacterial, antifungal, and antileishmanial agents
  6. Sonochemical synthesis of gold nanoparticles mediated by potato starch: Its performance in the treatment of esophageal cancer
  7. Computational study of ADME-Tox prediction of selected phytochemicals from Punica granatum peels
  8. Phytochemical analysis, in vitro antioxidant and antifungal activities of extracts and essential oil derived from Artemisia herba-alba Asso
  9. Two triazole-based coordination polymers: Synthesis and crystal structure characterization
  10. Phytochemical and physicochemical studies of different apple varieties grown in Morocco
  11. Synthesis of multi-template molecularly imprinted polymers (MT-MIPs) for isolating ethyl para-methoxycinnamate and ethyl cinnamate from Kaempferia galanga L., extract with methacrylic acid as functional monomer
  12. Nutraceutical potential of Mesembryanthemum forsskaolii Hochst. ex Bioss.: Insights into its nutritional composition, phytochemical contents, and antioxidant activity
  13. Evaluation of influence of Butea monosperma floral extract on inflammatory biomarkers
  14. Cannabis sativa L. essential oil: Chemical composition, anti-oxidant, anti-microbial properties, and acute toxicity: In vitro, in vivo, and in silico study
  15. The effect of gamma radiation on 5-hydroxymethylfurfural conversion in water and dimethyl sulfoxide
  16. Hollow mushroom nanomaterials for potentiometric sensing of Pb2+ ions in water via the intercalation of iodide ions into the polypyrrole matrix
  17. Determination of essential oil and chemical composition of St. John’s Wort
  18. Computational design and in vitro assay of lantadene-based novel inhibitors of NS3 protease of dengue virus
  19. Anti-parasitic activity and computational studies on a novel labdane diterpene from the roots of Vachellia nilotica
  20. Microbial dynamics and dehydrogenase activity in tomato (Lycopersicon esculentum Mill.) rhizospheres: Impacts on growth and soil health across different soil types
  21. Correlation between in vitro anti-urease activity and in silico molecular modeling approach of novel imidazopyridine–oxadiazole hybrids derivatives
  22. Spatial mapping of indoor air quality in a light metro system using the geographic information system method
  23. Iron indices and hemogram in renal anemia and the improvement with Tribulus terrestris green-formulated silver nanoparticles applied on rat model
  24. Integrated track of nano-informatics coupling with the enrichment concept in developing a novel nanoparticle targeting ERK protein in Naegleria fowleri
  25. Cytotoxic and phytochemical screening of Solanum lycopersicum–Daucus carota hydro-ethanolic extract and in silico evaluation of its lycopene content as anticancer agent
  26. Protective activities of silver nanoparticles containing Panax japonicus on apoptotic, inflammatory, and oxidative alterations in isoproterenol-induced cardiotoxicity
  27. pH-based colorimetric detection of monofunctional aldehydes in liquid and gas phases
  28. Investigating the effect of resveratrol on apoptosis and regulation of gene expression of Caco-2 cells: Unravelling potential implications for colorectal cancer treatment
  29. Metformin inhibits knee osteoarthritis induced by type 2 diabetes mellitus in rats: S100A8/9 and S100A12 as players and therapeutic targets
  30. Effect of silver nanoparticles formulated by Silybum marianum on menopausal urinary incontinence in ovariectomized rats
  31. Synthesis of new analogs of N-substituted(benzoylamino)-1,2,3,6-tetrahydropyridines
  32. Response of yield and quality of Japonica rice to different gradients of moisture deficit at grain-filling stage in cold regions
  33. Preparation of an inclusion complex of nickel-based β-cyclodextrin: Characterization and accelerating the osteoarthritis articular cartilage repair
  34. Empagliflozin-loaded nanomicelles responsive to reactive oxygen species for renal ischemia/reperfusion injury protection
  35. Preparation and pharmacodynamic evaluation of sodium aescinate solid lipid nanoparticles
  36. Assessment of potentially toxic elements and health risks of agricultural soil in Southwest Riyadh, Saudi Arabia
  37. Theoretical investigation of hydrogen-rich fuel production through ammonia decomposition
  38. Biosynthesis and screening of cobalt nanoparticles using citrus species for antimicrobial activity
  39. Investigating the interplay of genetic variations, MCP-1 polymorphism, and docking with phytochemical inhibitors for combatting dengue virus pathogenicity through in silico analysis
  40. Ultrasound induced biosynthesis of silver nanoparticles embedded into chitosan polymers: Investigation of its anti-cutaneous squamous cell carcinoma effects
  41. Copper oxide nanoparticles-mediated Heliotropium bacciferum leaf extract: Antifungal activity and molecular docking assays against strawberry pathogens
  42. Sprouted wheat flour for improving physical, chemical, rheological, microbial load, and quality properties of fino bread
  43. Comparative toxicity assessment of fisetin-aided artificial intelligence-assisted drug design targeting epibulbar dermoid through phytochemicals
  44. Acute toxicity and anti-inflammatory activity of bis-thiourea derivatives
  45. Anti-diabetic activity-guided isolation of α-amylase and α-glucosidase inhibitory terpenes from Capsella bursa-pastoris Linn.
  46. GC–MS analysis of Lactobacillus plantarum YW11 metabolites and its computational analysis on familial pulmonary fibrosis hub genes
  47. Green formulation of copper nanoparticles by Pistacia khinjuk leaf aqueous extract: Introducing a novel chemotherapeutic drug for the treatment of prostate cancer
  48. Improved photocatalytic properties of WO3 nanoparticles for Malachite green dye degradation under visible light irradiation: An effect of La doping
  49. One-pot synthesis of a network of Mn2O3–MnO2–poly(m-methylaniline) composite nanorods on a polypyrrole film presents a promising and efficient optoelectronic and solar cell device
  50. Groundwater quality and health risk assessment of nitrate and fluoride in Al Qaseem area, Saudi Arabia
  51. A comparative study of the antifungal efficacy and phytochemical composition of date palm leaflet extracts
  52. Processing of alcohol pomelo beverage (Citrus grandis (L.) Osbeck) using saccharomyces yeast: Optimization, physicochemical quality, and sensory characteristics
  53. Specialized compounds of four Cameroonian spices: Isolation, characterization, and in silico evaluation as prospective SARS-CoV-2 inhibitors
  54. Identification of a novel drug target in Porphyromonas gingivalis by a computational genome analysis approach
  55. Physico-chemical properties and durability of a fly-ash-based geopolymer
  56. FMS-like tyrosine kinase 3 inhibitory potentials of some phytochemicals from anti-leukemic plants using computational chemical methodologies
  57. Wild Thymus zygis L. ssp. gracilis and Eucalyptus camaldulensis Dehnh.: Chemical composition, antioxidant and antibacterial activities of essential oils
  58. 3D-QSAR, molecular docking, ADMET, simulation dynamic, and retrosynthesis studies on new styrylquinolines derivatives against breast cancer
  59. Deciphering the influenza neuraminidase inhibitory potential of naturally occurring biflavonoids: An in silico approach
  60. Determination of heavy elements in agricultural regions, Saudi Arabia
  61. Synthesis and characterization of antioxidant-enriched Moringa oil-based edible oleogel
  62. Ameliorative effects of thistle and thyme honeys on cyclophosphamide-induced toxicity in mice
  63. Study of phytochemical compound and antipyretic activity of Chenopodium ambrosioides L. fractions
  64. Investigating the adsorption mechanism of zinc chloride-modified porous carbon for sulfadiazine removal from water
  65. Performance repair of building materials using alumina and silica composite nanomaterials with electrodynamic properties
  66. Effects of nanoparticles on the activity and resistance genes of anaerobic digestion enzymes in livestock and poultry manure containing the antibiotic tetracycline
  67. Effect of copper nanoparticles green-synthesized using Ocimum basilicum against Pseudomonas aeruginosa in mice lung infection model
  68. Cardioprotective effects of nanoparticles green formulated by Spinacia oleracea extract on isoproterenol-induced myocardial infarction in mice by the determination of PPAR-γ/NF-κB pathway
  69. Anti-OTC antibody-conjugated fluorescent magnetic/silica and fluorescent hybrid silica nanoparticles for oxytetracycline detection
  70. Curcumin conjugated zinc nanoparticles for the treatment of myocardial infarction
  71. Identification and in silico screening of natural phloroglucinols as potential PI3Kα inhibitors: A computational approach for drug discovery
  72. Exploring the phytochemical profile and antioxidant evaluation: Molecular docking and ADMET analysis of main compounds from three Solanum species in Saudi Arabia
  73. Unveiling the molecular composition and biological properties of essential oil derived from the leaves of wild Mentha aquatica L.: A comprehensive in vitro and in silico exploration
  74. Analysis of bioactive compounds present in Boerhavia elegans seeds by GC-MS
  75. Homology modeling and molecular docking study of corticotrophin-releasing hormone: An approach to treat stress-related diseases
  76. LncRNA MIR17HG alleviates heart failure via targeting MIR17HG/miR-153-3p/SIRT1 axis in in vitro model
  77. Development and validation of a stability indicating UPLC-DAD method coupled with MS-TQD for ramipril and thymoquinone in bioactive SNEDDS with in silico toxicity analysis of ramipril degradation products
  78. Biosynthesis of Ag/Cu nanocomposite mediated by Curcuma longa: Evaluation of its antibacterial properties against oral pathogens
  79. Development of AMBER-compliant transferable force field parameters for polytetrafluoroethylene
  80. Treatment of gestational diabetes by Acroptilon repens leaf aqueous extract green-formulated iron nanoparticles in rats
  81. Development and characterization of new ecological adsorbents based on cardoon wastes: Application to brilliant green adsorption
  82. A fast, sensitive, greener, and stability-indicating HPLC method for the standardization and quantitative determination of chlorhexidine acetate in commercial products
  83. Assessment of Se, As, Cd, Cr, Hg, and Pb content status in Ankang tea plantations of China
  84. Effect of transition metal chloride (ZnCl2) on low-temperature pyrolysis of high ash bituminous coal
  85. Evaluating polyphenol and ascorbic acid contents, tannin removal ability, and physical properties during hydrolysis and convective hot-air drying of cashew apple powder
  86. Development and characterization of functional low-fat frozen dairy dessert enhanced with dried lemongrass powder
  87. Scrutinizing the effect of additive and synergistic antibiotics against carbapenem-resistant Pseudomonas aeruginosa
  88. Preparation, characterization, and determination of the therapeutic effects of copper nanoparticles green-formulated by Pistacia atlantica in diabetes-induced cardiac dysfunction in rat
  89. Antioxidant and antidiabetic potentials of methoxy-substituted Schiff bases using in vitro, in vivo, and molecular simulation approaches
  90. Anti-melanoma cancer activity and chemical profile of the essential oil of Seseli yunnanense Franch
  91. Molecular docking analysis of subtilisin-like alkaline serine protease (SLASP) and laccase with natural biopolymers
  92. Overcoming methicillin resistance by methicillin-resistant Staphylococcus aureus: Computational evaluation of napthyridine and oxadiazoles compounds for potential dual inhibition of PBP-2a and FemA proteins
  93. Exploring novel antitubercular agents: Innovative design of 2,3-diaryl-quinoxalines targeting DprE1 for effective tuberculosis treatment
  94. Drimia maritima flowers as a source of biologically potent components: Optimization of bioactive compound extractions, isolation, UPLC–ESI–MS/MS, and pharmacological properties
  95. Estimating molecular properties, drug-likeness, cardiotoxic risk, liability profile, and molecular docking study to characterize binding process of key phyto-compounds against serotonin 5-HT2A receptor
  96. Fabrication of β-cyclodextrin-based microgels for enhancing solubility of Terbinafine: An in-vitro and in-vivo toxicological evaluation
  97. Phyto-mediated synthesis of ZnO nanoparticles and their sunlight-driven photocatalytic degradation of cationic and anionic dyes
  98. Monosodium glutamate induces hypothalamic–pituitary–adrenal axis hyperactivation, glucocorticoid receptors down-regulation, and systemic inflammatory response in young male rats: Impact on miR-155 and miR-218
  99. Quality control analyses of selected honey samples from Serbia based on their mineral and flavonoid profiles, and the invertase activity
  100. Eco-friendly synthesis of silver nanoparticles using Phyllanthus niruri leaf extract: Assessment of antimicrobial activity, effectiveness on tropical neglected mosquito vector control, and biocompatibility using a fibroblast cell line model
  101. Green synthesis of silver nanoparticles containing Cichorium intybus to treat the sepsis-induced DNA damage in the liver of Wistar albino rats
  102. Quality changes of durian pulp (Durio ziberhinus Murr.) in cold storage
  103. Study on recrystallization process of nitroguanidine by directly adding cold water to control temperature
  104. Determination of heavy metals and health risk assessment in drinking water in Bukayriyah City, Saudi Arabia
  105. Larvicidal properties of essential oils of three Artemisia species against the chemically insecticide-resistant Nile fever vector Culex pipiens (L.) (Diptera: Culicidae): In vitro and in silico studies
  106. Design, synthesis, characterization, and theoretical calculations, along with in silico and in vitro antimicrobial proprieties of new isoxazole-amide conjugates
  107. The impact of drying and extraction methods on total lipid, fatty acid profile, and cytotoxicity of Tenebrio molitor larvae
  108. A zinc oxide–tin oxide–nerolidol hybrid nanomaterial: Efficacy against esophageal squamous cell carcinoma
  109. Research on technological process for production of muskmelon juice (Cucumis melo L.)
  110. Physicochemical components, antioxidant activity, and predictive models for quality of soursop tea (Annona muricata L.) during heat pump drying
  111. Characterization and application of Fe1−xCoxFe2O4 nanoparticles in Direct Red 79 adsorption
  112. Torilis arvensis ethanolic extract: Phytochemical analysis, antifungal efficacy, and cytotoxicity properties
  113. Magnetite–poly-1H pyrrole dendritic nanocomposite seeded on poly-1H pyrrole: A promising photocathode for green hydrogen generation from sanitation water without using external sacrificing agent
  114. HPLC and GC–MS analyses of phytochemical compounds in Haloxylon salicornicum extract: Antibacterial and antifungal activity assessment of phytopathogens
  115. Efficient and stable to coking catalysts of ethanol steam reforming comprised of Ni + Ru loaded on MgAl2O4 + LnFe0.7Ni0.3O3 (Ln = La, Pr) nanocomposites prepared via cost-effective procedure with Pluronic P123 copolymer
  116. Nitrogen and boron co-doped carbon dots probe for selectively detecting Hg2+ in water samples and the detection mechanism
  117. Heavy metals in road dust from typical old industrial areas of Wuhan: Seasonal distribution and bioaccessibility-based health risk assessment
  118. Phytochemical profiling and bioactivity evaluation of CBD- and THC-enriched Cannabis sativa extracts: In vitro and in silico investigation of antioxidant and anti-inflammatory effects
  119. Investigating dye adsorption: The role of surface-modified montmorillonite nanoclay in kinetics, isotherms, and thermodynamics
  120. Antimicrobial activity, induction of ROS generation in HepG2 liver cancer cells, and chemical composition of Pterospermum heterophyllum
  121. Study on the performance of nanoparticle-modified PVDF membrane in delaying membrane aging
  122. Impact of cholesterol in encapsulated vitamin E acetate within cocoliposomes
  123. Review Articles
  124. Structural aspects of Pt(η3-X1N1X2)(PL) (X1,2 = O, C, or Se) and Pt(η3-N1N2X1)(PL) (X1 = C, S, or Se) derivatives
  125. Biosurfactants in biocorrosion and corrosion mitigation of metals: An overview
  126. Stimulus-responsive MOF–hydrogel composites: Classification, preparation, characterization, and their advancement in medical treatments
  127. Electrochemical dissolution of titanium under alternating current polarization to obtain its dioxide
  128. Special Issue on Recent Trends in Green Chemistry
  129. Phytochemical screening and antioxidant activity of Vitex agnus-castus L.
  130. Phytochemical study, antioxidant activity, and dermoprotective activity of Chenopodium ambrosioides (L.)
  131. Exploitation of mangliculous marine fungi, Amarenographium solium, for the green synthesis of silver nanoparticles and their activity against multiple drug-resistant bacteria
  132. Study of the phytotoxicity of margines on Pistia stratiotes L.
  133. Special Issue on Advanced Nanomaterials for Energy, Environmental and Biological Applications - Part III
  134. Impact of biogenic zinc oxide nanoparticles on growth, development, and antioxidant system of high protein content crop (Lablab purpureus L.) sweet
  135. Green synthesis, characterization, and application of iron and molybdenum nanoparticles and their composites for enhancing the growth of Solanum lycopersicum
  136. Green synthesis of silver nanoparticles from Olea europaea L. extracted polysaccharides, characterization, and its assessment as an antimicrobial agent against multiple pathogenic microbes
  137. Photocatalytic treatment of organic dyes using metal oxides and nanocomposites: A quantitative study
  138. Antifungal, antioxidant, and photocatalytic activities of greenly synthesized iron oxide nanoparticles
  139. Special Issue on Phytochemical and Pharmacological Scrutinization of Medicinal Plants
  140. Hepatoprotective effects of safranal on acetaminophen-induced hepatotoxicity in rats
  141. Chemical composition and biological properties of Thymus capitatus plants from Algerian high plains: A comparative and analytical study
  142. Chemical composition and bioactivities of the methanol root extracts of Saussurea costus
  143. In vivo protective effects of vitamin C against cyto-genotoxicity induced by Dysphania ambrosioides aqueous extract
  144. Insights about the deleterious impact of a carbamate pesticide on some metabolic immune and antioxidant functions and a focus on the protective ability of a Saharan shrub and its anti-edematous property
  145. A comprehensive review uncovering the anticancerous potential of genkwanin (plant-derived compound) in several human carcinomas
  146. A study to investigate the anticancer potential of carvacrol via targeting Notch signaling in breast cancer
  147. Assessment of anti-diabetic properties of Ziziphus oenopolia (L.) wild edible fruit extract: In vitro and in silico investigations through molecular docking analysis
  148. Optimization of polyphenol extraction, phenolic profile by LC-ESI-MS/MS, antioxidant, anti-enzymatic, and cytotoxic activities of Physalis acutifolia
  149. Phytochemical screening, antioxidant properties, and photo-protective activities of Salvia balansae de Noé ex Coss
  150. Antihyperglycemic, antiglycation, anti-hypercholesteremic, and toxicity evaluation with gas chromatography mass spectrometry profiling for Aloe armatissima leaves
  151. Phyto-fabrication and characterization of gold nanoparticles by using Timur (Zanthoxylum armatum DC) and their effect on wound healing
  152. Does Erodium trifolium (Cav.) Guitt exhibit medicinal properties? Response elements from phytochemical profiling, enzyme-inhibiting, and antioxidant and antimicrobial activities
  153. Integrative in silico evaluation of the antiviral potential of terpenoids and its metal complexes derived from Homalomena aromatica based on main protease of SARS-CoV-2
  154. 6-Methoxyflavone improves anxiety, depression, and memory by increasing monoamines in mice brain: HPLC analysis and in silico studies
  155. Simultaneous extraction and quantification of hydrophilic and lipophilic antioxidants in Solanum lycopersicum L. varieties marketed in Saudi Arabia
  156. Biological evaluation of CH3OH and C2H5OH of Berberis vulgaris for in vivo antileishmanial potential against Leishmania tropica in murine models
https://doi.org/10.1515/chem-2023-0195
Keywords for this article
glycoconjugates; glycopyranosyl-α-trichloroacetimidates; glycosylation; antimicrobial; antileishmanial; molecular docking
Creative Commons
BY 4.0

Articles in the same Issue

  1. Regular Articles
  2. Porous silicon nanostructures: Synthesis, characterization, and their antifungal activity
  3. Biochar from de-oiled Chlorella vulgaris and its adsorption on antibiotics
  4. Phytochemicals profiling, in vitro and in vivo antidiabetic activity, and in silico studies on Ajuga iva (L.) Schreb.: A comprehensive approach
  5. Synthesis, characterization, in silico and in vitro studies of novel glycoconjugates as potential antibacterial, antifungal, and antileishmanial agents
  6. Sonochemical synthesis of gold nanoparticles mediated by potato starch: Its performance in the treatment of esophageal cancer
  7. Computational study of ADME-Tox prediction of selected phytochemicals from Punica granatum peels
  8. Phytochemical analysis, in vitro antioxidant and antifungal activities of extracts and essential oil derived from Artemisia herba-alba Asso
  9. Two triazole-based coordination polymers: Synthesis and crystal structure characterization
  10. Phytochemical and physicochemical studies of different apple varieties grown in Morocco
  11. Synthesis of multi-template molecularly imprinted polymers (MT-MIPs) for isolating ethyl para-methoxycinnamate and ethyl cinnamate from Kaempferia galanga L., extract with methacrylic acid as functional monomer
  12. Nutraceutical potential of Mesembryanthemum forsskaolii Hochst. ex Bioss.: Insights into its nutritional composition, phytochemical contents, and antioxidant activity
  13. Evaluation of influence of Butea monosperma floral extract on inflammatory biomarkers
  14. Cannabis sativa L. essential oil: Chemical composition, anti-oxidant, anti-microbial properties, and acute toxicity: In vitro, in vivo, and in silico study
  15. The effect of gamma radiation on 5-hydroxymethylfurfural conversion in water and dimethyl sulfoxide
  16. Hollow mushroom nanomaterials for potentiometric sensing of Pb2+ ions in water via the intercalation of iodide ions into the polypyrrole matrix
  17. Determination of essential oil and chemical composition of St. John’s Wort
  18. Computational design and in vitro assay of lantadene-based novel inhibitors of NS3 protease of dengue virus
  19. Anti-parasitic activity and computational studies on a novel labdane diterpene from the roots of Vachellia nilotica
  20. Microbial dynamics and dehydrogenase activity in tomato (Lycopersicon esculentum Mill.) rhizospheres: Impacts on growth and soil health across different soil types
  21. Correlation between in vitro anti-urease activity and in silico molecular modeling approach of novel imidazopyridine–oxadiazole hybrids derivatives
  22. Spatial mapping of indoor air quality in a light metro system using the geographic information system method
  23. Iron indices and hemogram in renal anemia and the improvement with Tribulus terrestris green-formulated silver nanoparticles applied on rat model
  24. Integrated track of nano-informatics coupling with the enrichment concept in developing a novel nanoparticle targeting ERK protein in Naegleria fowleri
  25. Cytotoxic and phytochemical screening of Solanum lycopersicum–Daucus carota hydro-ethanolic extract and in silico evaluation of its lycopene content as anticancer agent
  26. Protective activities of silver nanoparticles containing Panax japonicus on apoptotic, inflammatory, and oxidative alterations in isoproterenol-induced cardiotoxicity
  27. pH-based colorimetric detection of monofunctional aldehydes in liquid and gas phases
  28. Investigating the effect of resveratrol on apoptosis and regulation of gene expression of Caco-2 cells: Unravelling potential implications for colorectal cancer treatment
  29. Metformin inhibits knee osteoarthritis induced by type 2 diabetes mellitus in rats: S100A8/9 and S100A12 as players and therapeutic targets
  30. Effect of silver nanoparticles formulated by Silybum marianum on menopausal urinary incontinence in ovariectomized rats
  31. Synthesis of new analogs of N-substituted(benzoylamino)-1,2,3,6-tetrahydropyridines
  32. Response of yield and quality of Japonica rice to different gradients of moisture deficit at grain-filling stage in cold regions
  33. Preparation of an inclusion complex of nickel-based β-cyclodextrin: Characterization and accelerating the osteoarthritis articular cartilage repair
  34. Empagliflozin-loaded nanomicelles responsive to reactive oxygen species for renal ischemia/reperfusion injury protection
  35. Preparation and pharmacodynamic evaluation of sodium aescinate solid lipid nanoparticles
  36. Assessment of potentially toxic elements and health risks of agricultural soil in Southwest Riyadh, Saudi Arabia
  37. Theoretical investigation of hydrogen-rich fuel production through ammonia decomposition
  38. Biosynthesis and screening of cobalt nanoparticles using citrus species for antimicrobial activity
  39. Investigating the interplay of genetic variations, MCP-1 polymorphism, and docking with phytochemical inhibitors for combatting dengue virus pathogenicity through in silico analysis
  40. Ultrasound induced biosynthesis of silver nanoparticles embedded into chitosan polymers: Investigation of its anti-cutaneous squamous cell carcinoma effects
  41. Copper oxide nanoparticles-mediated Heliotropium bacciferum leaf extract: Antifungal activity and molecular docking assays against strawberry pathogens
  42. Sprouted wheat flour for improving physical, chemical, rheological, microbial load, and quality properties of fino bread
  43. Comparative toxicity assessment of fisetin-aided artificial intelligence-assisted drug design targeting epibulbar dermoid through phytochemicals
  44. Acute toxicity and anti-inflammatory activity of bis-thiourea derivatives
  45. Anti-diabetic activity-guided isolation of α-amylase and α-glucosidase inhibitory terpenes from Capsella bursa-pastoris Linn.
  46. GC–MS analysis of Lactobacillus plantarum YW11 metabolites and its computational analysis on familial pulmonary fibrosis hub genes
  47. Green formulation of copper nanoparticles by Pistacia khinjuk leaf aqueous extract: Introducing a novel chemotherapeutic drug for the treatment of prostate cancer
  48. Improved photocatalytic properties of WO3 nanoparticles for Malachite green dye degradation under visible light irradiation: An effect of La doping
  49. One-pot synthesis of a network of Mn2O3–MnO2–poly(m-methylaniline) composite nanorods on a polypyrrole film presents a promising and efficient optoelectronic and solar cell device
  50. Groundwater quality and health risk assessment of nitrate and fluoride in Al Qaseem area, Saudi Arabia
  51. A comparative study of the antifungal efficacy and phytochemical composition of date palm leaflet extracts
  52. Processing of alcohol pomelo beverage (Citrus grandis (L.) Osbeck) using saccharomyces yeast: Optimization, physicochemical quality, and sensory characteristics
  53. Specialized compounds of four Cameroonian spices: Isolation, characterization, and in silico evaluation as prospective SARS-CoV-2 inhibitors
  54. Identification of a novel drug target in Porphyromonas gingivalis by a computational genome analysis approach
  55. Physico-chemical properties and durability of a fly-ash-based geopolymer
  56. FMS-like tyrosine kinase 3 inhibitory potentials of some phytochemicals from anti-leukemic plants using computational chemical methodologies
  57. Wild Thymus zygis L. ssp. gracilis and Eucalyptus camaldulensis Dehnh.: Chemical composition, antioxidant and antibacterial activities of essential oils
  58. 3D-QSAR, molecular docking, ADMET, simulation dynamic, and retrosynthesis studies on new styrylquinolines derivatives against breast cancer
  59. Deciphering the influenza neuraminidase inhibitory potential of naturally occurring biflavonoids: An in silico approach
  60. Determination of heavy elements in agricultural regions, Saudi Arabia
  61. Synthesis and characterization of antioxidant-enriched Moringa oil-based edible oleogel
  62. Ameliorative effects of thistle and thyme honeys on cyclophosphamide-induced toxicity in mice
  63. Study of phytochemical compound and antipyretic activity of Chenopodium ambrosioides L. fractions
  64. Investigating the adsorption mechanism of zinc chloride-modified porous carbon for sulfadiazine removal from water
  65. Performance repair of building materials using alumina and silica composite nanomaterials with electrodynamic properties
  66. Effects of nanoparticles on the activity and resistance genes of anaerobic digestion enzymes in livestock and poultry manure containing the antibiotic tetracycline
  67. Effect of copper nanoparticles green-synthesized using Ocimum basilicum against Pseudomonas aeruginosa in mice lung infection model
  68. Cardioprotective effects of nanoparticles green formulated by Spinacia oleracea extract on isoproterenol-induced myocardial infarction in mice by the determination of PPAR-γ/NF-κB pathway
  69. Anti-OTC antibody-conjugated fluorescent magnetic/silica and fluorescent hybrid silica nanoparticles for oxytetracycline detection
  70. Curcumin conjugated zinc nanoparticles for the treatment of myocardial infarction
  71. Identification and in silico screening of natural phloroglucinols as potential PI3Kα inhibitors: A computational approach for drug discovery
  72. Exploring the phytochemical profile and antioxidant evaluation: Molecular docking and ADMET analysis of main compounds from three Solanum species in Saudi Arabia
  73. Unveiling the molecular composition and biological properties of essential oil derived from the leaves of wild Mentha aquatica L.: A comprehensive in vitro and in silico exploration
  74. Analysis of bioactive compounds present in Boerhavia elegans seeds by GC-MS
  75. Homology modeling and molecular docking study of corticotrophin-releasing hormone: An approach to treat stress-related diseases
  76. LncRNA MIR17HG alleviates heart failure via targeting MIR17HG/miR-153-3p/SIRT1 axis in in vitro model
  77. Development and validation of a stability indicating UPLC-DAD method coupled with MS-TQD for ramipril and thymoquinone in bioactive SNEDDS with in silico toxicity analysis of ramipril degradation products
  78. Biosynthesis of Ag/Cu nanocomposite mediated by Curcuma longa: Evaluation of its antibacterial properties against oral pathogens
  79. Development of AMBER-compliant transferable force field parameters for polytetrafluoroethylene
  80. Treatment of gestational diabetes by Acroptilon repens leaf aqueous extract green-formulated iron nanoparticles in rats
  81. Development and characterization of new ecological adsorbents based on cardoon wastes: Application to brilliant green adsorption
  82. A fast, sensitive, greener, and stability-indicating HPLC method for the standardization and quantitative determination of chlorhexidine acetate in commercial products
  83. Assessment of Se, As, Cd, Cr, Hg, and Pb content status in Ankang tea plantations of China
  84. Effect of transition metal chloride (ZnCl2) on low-temperature pyrolysis of high ash bituminous coal
  85. Evaluating polyphenol and ascorbic acid contents, tannin removal ability, and physical properties during hydrolysis and convective hot-air drying of cashew apple powder
  86. Development and characterization of functional low-fat frozen dairy dessert enhanced with dried lemongrass powder
  87. Scrutinizing the effect of additive and synergistic antibiotics against carbapenem-resistant Pseudomonas aeruginosa
  88. Preparation, characterization, and determination of the therapeutic effects of copper nanoparticles green-formulated by Pistacia atlantica in diabetes-induced cardiac dysfunction in rat
  89. Antioxidant and antidiabetic potentials of methoxy-substituted Schiff bases using in vitro, in vivo, and molecular simulation approaches
  90. Anti-melanoma cancer activity and chemical profile of the essential oil of Seseli yunnanense Franch
  91. Molecular docking analysis of subtilisin-like alkaline serine protease (SLASP) and laccase with natural biopolymers
  92. Overcoming methicillin resistance by methicillin-resistant Staphylococcus aureus: Computational evaluation of napthyridine and oxadiazoles compounds for potential dual inhibition of PBP-2a and FemA proteins
  93. Exploring novel antitubercular agents: Innovative design of 2,3-diaryl-quinoxalines targeting DprE1 for effective tuberculosis treatment
  94. Drimia maritima flowers as a source of biologically potent components: Optimization of bioactive compound extractions, isolation, UPLC–ESI–MS/MS, and pharmacological properties
  95. Estimating molecular properties, drug-likeness, cardiotoxic risk, liability profile, and molecular docking study to characterize binding process of key phyto-compounds against serotonin 5-HT2A receptor
  96. Fabrication of β-cyclodextrin-based microgels for enhancing solubility of Terbinafine: An in-vitro and in-vivo toxicological evaluation
  97. Phyto-mediated synthesis of ZnO nanoparticles and their sunlight-driven photocatalytic degradation of cationic and anionic dyes
  98. Monosodium glutamate induces hypothalamic–pituitary–adrenal axis hyperactivation, glucocorticoid receptors down-regulation, and systemic inflammatory response in young male rats: Impact on miR-155 and miR-218
  99. Quality control analyses of selected honey samples from Serbia based on their mineral and flavonoid profiles, and the invertase activity
  100. Eco-friendly synthesis of silver nanoparticles using Phyllanthus niruri leaf extract: Assessment of antimicrobial activity, effectiveness on tropical neglected mosquito vector control, and biocompatibility using a fibroblast cell line model
  101. Green synthesis of silver nanoparticles containing Cichorium intybus to treat the sepsis-induced DNA damage in the liver of Wistar albino rats
  102. Quality changes of durian pulp (Durio ziberhinus Murr.) in cold storage
  103. Study on recrystallization process of nitroguanidine by directly adding cold water to control temperature
  104. Determination of heavy metals and health risk assessment in drinking water in Bukayriyah City, Saudi Arabia
  105. Larvicidal properties of essential oils of three Artemisia species against the chemically insecticide-resistant Nile fever vector Culex pipiens (L.) (Diptera: Culicidae): In vitro and in silico studies
  106. Design, synthesis, characterization, and theoretical calculations, along with in silico and in vitro antimicrobial proprieties of new isoxazole-amide conjugates
  107. The impact of drying and extraction methods on total lipid, fatty acid profile, and cytotoxicity of Tenebrio molitor larvae
  108. A zinc oxide–tin oxide–nerolidol hybrid nanomaterial: Efficacy against esophageal squamous cell carcinoma
  109. Research on technological process for production of muskmelon juice (Cucumis melo L.)
  110. Physicochemical components, antioxidant activity, and predictive models for quality of soursop tea (Annona muricata L.) during heat pump drying
  111. Characterization and application of Fe1−xCoxFe2O4 nanoparticles in Direct Red 79 adsorption
  112. Torilis arvensis ethanolic extract: Phytochemical analysis, antifungal efficacy, and cytotoxicity properties
  113. Magnetite–poly-1H pyrrole dendritic nanocomposite seeded on poly-1H pyrrole: A promising photocathode for green hydrogen generation from sanitation water without using external sacrificing agent
  114. HPLC and GC–MS analyses of phytochemical compounds in Haloxylon salicornicum extract: Antibacterial and antifungal activity assessment of phytopathogens
  115. Efficient and stable to coking catalysts of ethanol steam reforming comprised of Ni + Ru loaded on MgAl2O4 + LnFe0.7Ni0.3O3 (Ln = La, Pr) nanocomposites prepared via cost-effective procedure with Pluronic P123 copolymer
  116. Nitrogen and boron co-doped carbon dots probe for selectively detecting Hg2+ in water samples and the detection mechanism
  117. Heavy metals in road dust from typical old industrial areas of Wuhan: Seasonal distribution and bioaccessibility-based health risk assessment
  118. Phytochemical profiling and bioactivity evaluation of CBD- and THC-enriched Cannabis sativa extracts: In vitro and in silico investigation of antioxidant and anti-inflammatory effects
  119. Investigating dye adsorption: The role of surface-modified montmorillonite nanoclay in kinetics, isotherms, and thermodynamics
  120. Antimicrobial activity, induction of ROS generation in HepG2 liver cancer cells, and chemical composition of Pterospermum heterophyllum
  121. Study on the performance of nanoparticle-modified PVDF membrane in delaying membrane aging
  122. Impact of cholesterol in encapsulated vitamin E acetate within cocoliposomes
  123. Review Articles
  124. Structural aspects of Pt(η3-X1N1X2)(PL) (X1,2 = O, C, or Se) and Pt(η3-N1N2X1)(PL) (X1 = C, S, or Se) derivatives
  125. Biosurfactants in biocorrosion and corrosion mitigation of metals: An overview
  126. Stimulus-responsive MOF–hydrogel composites: Classification, preparation, characterization, and their advancement in medical treatments
  127. Electrochemical dissolution of titanium under alternating current polarization to obtain its dioxide
  128. Special Issue on Recent Trends in Green Chemistry
  129. Phytochemical screening and antioxidant activity of Vitex agnus-castus L.
  130. Phytochemical study, antioxidant activity, and dermoprotective activity of Chenopodium ambrosioides (L.)
  131. Exploitation of mangliculous marine fungi, Amarenographium solium, for the green synthesis of silver nanoparticles and their activity against multiple drug-resistant bacteria
  132. Study of the phytotoxicity of margines on Pistia stratiotes L.
  133. Special Issue on Advanced Nanomaterials for Energy, Environmental and Biological Applications - Part III
  134. Impact of biogenic zinc oxide nanoparticles on growth, development, and antioxidant system of high protein content crop (Lablab purpureus L.) sweet
  135. Green synthesis, characterization, and application of iron and molybdenum nanoparticles and their composites for enhancing the growth of Solanum lycopersicum
  136. Green synthesis of silver nanoparticles from Olea europaea L. extracted polysaccharides, characterization, and its assessment as an antimicrobial agent against multiple pathogenic microbes
  137. Photocatalytic treatment of organic dyes using metal oxides and nanocomposites: A quantitative study
  138. Antifungal, antioxidant, and photocatalytic activities of greenly synthesized iron oxide nanoparticles
  139. Special Issue on Phytochemical and Pharmacological Scrutinization of Medicinal Plants
  140. Hepatoprotective effects of safranal on acetaminophen-induced hepatotoxicity in rats
  141. Chemical composition and biological properties of Thymus capitatus plants from Algerian high plains: A comparative and analytical study
  142. Chemical composition and bioactivities of the methanol root extracts of Saussurea costus
  143. In vivo protective effects of vitamin C against cyto-genotoxicity induced by Dysphania ambrosioides aqueous extract
  144. Insights about the deleterious impact of a carbamate pesticide on some metabolic immune and antioxidant functions and a focus on the protective ability of a Saharan shrub and its anti-edematous property
  145. A comprehensive review uncovering the anticancerous potential of genkwanin (plant-derived compound) in several human carcinomas
  146. A study to investigate the anticancer potential of carvacrol via targeting Notch signaling in breast cancer
  147. Assessment of anti-diabetic properties of Ziziphus oenopolia (L.) wild edible fruit extract: In vitro and in silico investigations through molecular docking analysis
  148. Optimization of polyphenol extraction, phenolic profile by LC-ESI-MS/MS, antioxidant, anti-enzymatic, and cytotoxic activities of Physalis acutifolia
  149. Phytochemical screening, antioxidant properties, and photo-protective activities of Salvia balansae de Noé ex Coss
  150. Antihyperglycemic, antiglycation, anti-hypercholesteremic, and toxicity evaluation with gas chromatography mass spectrometry profiling for Aloe armatissima leaves
  151. Phyto-fabrication and characterization of gold nanoparticles by using Timur (Zanthoxylum armatum DC) and their effect on wound healing
  152. Does Erodium trifolium (Cav.) Guitt exhibit medicinal properties? Response elements from phytochemical profiling, enzyme-inhibiting, and antioxidant and antimicrobial activities
  153. Integrative in silico evaluation of the antiviral potential of terpenoids and its metal complexes derived from Homalomena aromatica based on main protease of SARS-CoV-2
  154. 6-Methoxyflavone improves anxiety, depression, and memory by increasing monoamines in mice brain: HPLC analysis and in silico studies
  155. Simultaneous extraction and quantification of hydrophilic and lipophilic antioxidants in Solanum lycopersicum L. varieties marketed in Saudi Arabia
  156. Biological evaluation of CH3OH and C2H5OH of Berberis vulgaris for in vivo antileishmanial potential against Leishmania tropica in murine models
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 20.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/chem-2023-0195/html
Scroll to top button