Home Deciphering the influenza neuraminidase inhibitory potential of naturally occurring biflavonoids: An in silico approach
Article Open Access

Deciphering the influenza neuraminidase inhibitory potential of naturally occurring biflavonoids: An in silico approach

  • Kolade O. Faloye ORCID logo EMAIL logo , Shaban Ahmad ORCID logo , Olubunmi T. Oyasowo , Esther O. Shalom , Nagmi Bano , Esther A. Olanudun , Tawakalit O. Kelani , Habeeb E. Aliyu , Khalid Raza ORCID logo EMAIL logo , Boluwaji I. Makinde and Abdullah R. Alanzi EMAIL logo
Published/Copyright: June 26, 2024
Download Article (PDF)
Open Chemistry
From the journal Open Chemistry Volume 22 Issue 1

Abstract

Influenza infection poses a significant threat to the existence of humans and animals. Its inhibition by secondary metabolites may proffer a lasting solution to its resistance to available synthetic therapeutic agents. In this study, we investigated the influenza neuraminidase (NA) inhibitory potential of naturally occurring C–O–C biflavonoids using integrated computational approaches. The molecular docking method was employed to identify biflavonoids with high binding affinities, and molecular dynamics simulation was performed for 100 ns to examine the stability, binding mode, and interactions elicited by the hit molecules in influenza NA-binding pocket. The bioavailability and pharmacokinetic properties of the hit biflavonoids were examined using swissADME. The molecular docking studies identified lophirone L, delicaflavone, lanaroflavone, pulvinatabiflavone, and ochnaflavone as the hit molecules with the binding affinity of −9.9 to −9.3 kcal/mol. The root means square deviation and root mean square fluctuation plots obtained from the molecular dynamics simulation showed that the selected biflavonoids were reasonably stable at the enzyme’s binding pocket. The ADMET studies showed that the top-ranked biflavonoids exhibit good pharmacokinetic and bioavailability properties. Furthermore, the density functional theory studies showed that the selected hit secondary metabolite possesses good pharmacological properties. Thus, the inhibitory activities of these compounds on viral neuraminidase could be helpful in the management of influenza infections.

Keywords: influenza; influenza neuraminidase; molecular docking; molecular dynamics simulation; bioavailability

1 Introduction

Influenza is an acute respiratory infection caused by negative-stranded RNA influenza viruses and presents with significant complications like myocarditis, encephalitis, and multiple organ failure [1,2]. Influenza’s life cycle has fundamental glycoproteins like neuraminidase (NA) and hemagglutinin (HA) [3]. The NA cleaves sialic acid residues on cellular receptors, thereby facilitating the release of newly produced virions, while HA binds to host cell receptors, thereby promoting infection transmission [4,5]. In the 1970s, influenza NA was identified as a viable drug target which marked a crucial turning point in influenza-focused research [6]. Subsequent to the NA discovery, two standard drugs were developed for influenza management. The first neuraminidase inhibitor (NAI), zanamivir, was introduced, but its efficacy was hampered by a low absolute bioavailability [7,8]. Also, another NAI, oseltamivir was developed to address this bioavailability issue, but its use was limited by the resistance of influenza viruses to its therapeutic efficiency. The deficiencies of these drugs have promoted the search for novel therapeutic options characterized by good bioavailability and resistance mitigation [9,10].

Natural products are major sources of therapeutic agents and have proven effective against deadly diseases including viral and microbial infections [11,12,13]. Biflavonoids, also known as dimeric flavonoids, are polyphenolic secondary metabolites found in medicinal plants [14]. These plant-derived chemical compounds comprise those linked by a C–C or C–O–C bond between their phenyl-chromenone units (Figure 1) [15]. Biflavonoids connected via the C–O–C bond have shown remarkable pharmacological attributes like antioxidant, anti-inflammatory, anticancer, antiviral, antiparasitic, and hepatoprotective properties [15,16,17,18]. The major source of C–O–C biflavonoids include plants like Rhus succedanea, Selaginella tamariscina, Lophira alata, Ginkgo biloba, and Campnosperma panamense [19,20,21,22,23].

Figure 1 General structure of C–O–C-linked biflavonoids.
Figure 1

General structure of C–O–C-linked biflavonoids.

Computer-aided drug design is among the major innovative approaches developed to identify new drug leads that can effectively treat diseases [24]. Molecular docking is an efficient technique used to select a hit molecule through the prediction of its binding affinity against a disease target [24,25]. Molecular dynamic simulation is another method that helps to assess the stability, interactions of potential drug candidates, and their binding mode with specific target proteins [26]. Computational methods like molecular docking, molecular dynamics simulation, and density functional theory play a pivotal role in modern drug development. Several studies have established the efficacy of flavonoids and biflavonoids as potent antiviral agents [18,27,28]. However, the inhibitory property of naturally occurring C–O–C-linked biflavonoids is yet to be evaluated. Herein, we investigate the inhibitory potential of plant-derived C–O–C biflavonoids against influenza NA using integrated molecular docking and molecular dynamics simulation approaches.

2 Methodology

We have plotted a graphical abstract in Figure 2 to show the methodology and how we proceeded with the analysis of targeting influenza with multiple C–O–C biflavonoids drugs. We successfully identified and probed their effectiveness in computational experimentations. Furthermore, the detailed methods are as follows.

Figure 2 Showing the graphical abstract of the study from conceptualization to identifying and validation using the computational approaches.
Figure 2

Showing the graphical abstract of the study from conceptualization to identifying and validation using the computational approaches.

2.1 Protein and ligand preparation

The 3D crystallographic structure of influenza NA (PDBID: 3TI5) [29] was retrieved from the protein data bank (www.rcsb.org) and loaded on PyMol software to remove the water molecules, co-factors, and ions. The native ligand (zanamivir) was also identified on PyMol software, and the residues within 5 Å resident at the protein binding site were selected. Later on, the native ligand was removed to obtain a clean protein. The protein was saved in a PDB format for docking purposes.

The chemical structures of the 20 naturally occurring C–O–C biflavonoids (see supplementary material, Table S1) were built with Spartan 14 software, while the standard drugs (zanamivir and oseltamivir) were downloaded from the PubChem database (https://pub-chem.ncbi.nlm.nih.gov/). All the chemical structures were saved in an SDF format and loaded into Open Babel for energy minimization. Then, the energy-minimized ligands were saved in PDBQT format.

2.2 Molecular docking studies

The docking methodology was first validated by re-docking the native ligand in the binding pocket of influenza NA and estimating its root means square deviation (RMSD) value. The molecular docking studies of the C–O–C biflavonoids, zanamivir and oseltamivir, against influenza NA were done by converting the clean protein’s PDB file to PDBQT using the MGL software. After that, the protein was loaded into the Autodock Vina interface of PyRx 0.8 software [30] and amino acid residues (Arg118, Glu119, Leu134, Arg151, Arg152, Arg156, Trp178, Ser179, Ile222, Arg224, Glu227, Ser246, Glu276, Glu277, Arg292, Asn294, Gly348, Arg371, Tyr406) resident within 5 Å was selected. Then, the grid box of the protein was adjusted to center_x = 66.2633, center_y = 15.9425, and center_z = −0.7511 and size_x = 27.3432, size_y = 17.5309, and size_z = 25.8509. The PDBQT file of the biflavonoids, zanamivir and oseltamivir, was loaded, and molecular docking was carried out against influenza NA at an exhaustiveness of 100. After successfully completing the docking procedure, the binding poses of the ligand were retrieved, and those with the lowest RMSD value were selected for hydrogen bonding, hydrophobic, and pi-interaction analysis using the Discovery Studio Visualizer software.

2.3 Molecular interaction fingerprints (IFP) and pharmacokinetic studies

The molecular IFP was computed using the IFPs tool in Schrödinger Maestro, where we selected each complex, checked the receptor–ligand complex option, and kept to any contact types. We directly computed the fingerprints as the protein was the same, so it was unnecessary to align the sequences. Any contact type and color main plot were kept to make it clearer, and it was further enhanced by keeping only interacting residues, and the ligand display property was kept to the docking score to interpret it better [31,32,33]. Furthermore, the pharmacokinetic properties of the potential influenza NAIs were assessed using the SwissADME (http://www.swissadme.ch/) and pkCSM (http://www.biosig.lab.uq.edu.au/pkcsm/) online servers. Parameters such as solubility, human intestinal absorption, hepatotoxicity, bioavailability, and the secondary metabolites’ carcinogenic properties were considered to understand their druggable potentials.

2.4 Density functional theory studies

In drug design, density functional theory (DFT) stands for density functional theory, a computational quantum mechanical method used to study the electronic structure of molecules. DFT analysis helps us understand how electrons are distributed in a molecular system, providing crucial insights into various molecular properties, and in drug designing, DFT is employed to delve into the energetics and electronic properties of drug molecules and their interactions with target proteins. We can gain insights into potential drug candidates’ stability, reactivity, and binding affinity by calculating electronic densities and energy levels. DFT analysis allows us to predict molecular properties such as molecular orbitals, electron density distribution, and electrostatic potential. These predictions are vital for understanding how drugs behave at the molecular level. The DFT calculations of the hit secondary metabolites were performed with the Spartan 14 program using functional B3LYP with a 6-31G basis set [34]. In these calculations, the frontier orbital parameters like energy gap (ΔE gap), chemical reactivity (µ), electrophilicity index (ω), and electronegativity (χ) were estimated.

(1) Δ E gap = E LUMO – E HOMO ,

(2) µ = 1 2 ( E HOMO + E LUMO ) ,

(3) ω = μ 2 2 η ,

(4) χ = − μ .

2.5 Molecular dynamic (MD) simulation

The MD simulations of the docked complexes were performed using the academic version of DE Shaw’s Desmond [35]. The system builder tool was used to prepare the system model in which we have used the SPC water model in orthorhombic conditions with 10 × 10 × 10 Å distances in buffer conditions. 3Na+ was added to each complex to neutralize the system as all of them had the net charge of −3 and then excluded ion and salt placement within 20 Å before minimization of volume to have a properly fitted neutralized system. Furthermore, the OPLS4 forcefield was used to minimize the complete system. The MD simulation was performed using the molecular dynamic panel for 100 ns with a recording interval of 100 ps that generated a total of 1,000 frames at 300 K temperature with 1.01325 bar pressure and was kept in the NPT ensemble to produce the trajectories that were further analyzed with the simulation interaction diagram tool [36,37].

3 Results

3.1 Molecular docking studies

The docking methodology adopted for the study was validated, and an RMSD value of less than 2 was obtained, indicating that the method developed is reproducible. The docking studies explored the ligand with the favorable binding affinity with the active binding site of influenza NA. The result revealed that all selected hit molecules displayed excellent docking scores ranging from −9.3 to −9.9 kcal/mol compared to zanamivir and oseltamivir that elicited the binding affinity of −7.9 and −6.1 kcal/mol as shown in Table 1.

Table 1

Interaction analysis of the hit biflavonoids against influenza NA

Ligand Binding energy kcal/mol Hydrogen bond Hydrophobic interaction Pi-interaction Electrostatic interaction
Amino acid Distance (Å)
Lophirone L −9.9 Glu227 2.1238 Arg224, Arg371, Ile421, Pro431, Lys432 Arg224, Arg371, Ile421, Pro431, Lys432 Asp151, Arg292, Arg371
Arg292 2.6414
Arg371 1.9069
Arg371 2.0590
Arg371 2.0902
Trp406 2.4209
Trp406 2.8049
Delicaflavone −9.6 Trp178 2.4947 Arg224, Arg371, Pro431 Arg224, Arg371, Pro431 Asp151, Glu277, Arg371
Ser370 2.4658
Lanaroflavone −9.5 Trp178 2.3234 Ile149, Arg224, Pro431 Ile149, Arg224, Pro431 Arg118, Glu277, Arg371
Asn347 1.9884
Pulvinatabiflavone −9.4 Ser246 2.3614 Arg371, Ile427, Pro431, Lys432 Arg371, Ile427, Pro431, Lys432 Glu276, Arg371
Arg292 2.9499
Ile427 2.7219
Ochnaflavone −9.3 Ser246 2.1059 Pro236, Arg371, Ile427, Pro431, Lys432 Pro236, Arg371, Ile427, Pro431, Lys432 Glu276, Arg371
Glu277 2.1095
Arg292 2.5537
Arg371 2.4347

Lophirone L isolated from L. alata leaves elicited the best binding affinity against influenza NA at −9.9 kcal/mol. The hydrogen atoms on the biflavonoid established good hydrogen bond interaction with Glu227 at 2.1238 Å, Arg371 at 1.9069 Å, and Trp406 at 2.4209 and 2.8049 Å. Also, the oxygen atoms on the phytochemical moiety formed hydrogen bonds with Arg292 at 2.6414 Å, Arg371 at 2.0590 and 2.0902 Å, and Trp406 at 1.9069 Å, respectively. It was further stabilized at the influenza NA binding site by participating in hydrophobic and pi-interactions (pi-alkyl) with Arg224, Arg371, lle427, Pro431, and Lys432. Furthermore, electrostatic interactions were observed between the ligand and amino acid residues like Asp151, Arg292, and Arg371 (Figure 3c, Table 1). Delicaflavone obtained from L. alata was identified as the second-best ligand with a binding affinity of −9.6 kcal/mol. The hydrogen atoms on the delicaflavone moiety participated in hydrogen bond interactions with Tyr178 at 2.4947 Å and Ser370 at 2.4658 Å. The polyphenolic phytochemical was further stabilized at hydrophobic and pi-interactions (pi-alkyl) with Arg224, Arg371, and Pro431. Also, electrostatic interactions were established between the amino acid residues resident at the active site of the hit biflavonoid and Asp151, Glu277, and Arg371 (Figure 3a, Table 1). Lanaroflavone isolated from C. panamense was selected as the third-best hit phytochemical against the enzyme, with a binding affinity of −9.5 kcal/mol. The potential influenza NAI established hydrogen bond interactions with Trp178 at 2.3234 Å and Asn347 at 1.9884 Å. Also, the ligand attained stability at the enzyme’s binding pocket by forming hydrophobic and pi-interactions with Ile149, Arg224, and Pro431. Additionally, electrostatic interactions were observed between the ligand and Glu276 and Arg371 (Figure 3b, Table 1). Pulvinatabiflavone obtained from S. tamariscina elicited a binding affinity of −9.4 kcal/mol and was selected as the fourth-best-hit molecule. The oxygen and hydrogen atoms on the polyphenolic phytochemical participated in hydrogen bond interaction with Arg292 at 2.9499 Å, Ser246 at 2.3614 Å, and Ile427 at 2.7219 Å. Pulvinatabiflavone was stabilized at the influenza NA binding pocket by forming hydrophobic and pi-interactions with Arg371, Ile427, Pro431, and Lys432. Furthermore, electrostatic interactions were identified between the phytochemical and Glu276 and Arg371, respectively (Figure 3e, Table 1). Ochnaflavone isolated from Ochna pretoriensis was selected as the fifth-best influenza NAI as it gave a binding affinity of −9.3 kcal/mol. The oxygen and hydrogen atoms on the hit biflavonoid formed hydrogen bond interactions with Arg292 at 2.5537 Å, Ser246 at 2.1059 Å, Arg371 at 2.4347 Å, and Glu277 at 2.1095 Å. Ochnaflavone was further stabilized by participating in hydrophobic and pi-interactions with Pro236, Arg371, Ile427, Pro431, and Lys432. Also, electrostatic interactions were observed between the polyphenolic compound and Glu276 and Arg371 (Figure 3d, Table 1).

Figure 3 Showing the docked pose in 3D and 2D for 3TI5 with (a) delicaflavone, (b) lanaroflavone, (c) lophirone, (d) ochnaflavone, and (e) pulvinatabiflavone.
Figure 3

Showing the docked pose in 3D and 2D for 3TI5 with (a) delicaflavone, (b) lanaroflavone, (c) lophirone, (d) ochnaflavone, and (e) pulvinatabiflavone.

3.2 Molecular IFP and pharmacokinetic analysis

Molecular IFP is a computational method that encodes molecular interactions. Its importance lies in characterizing and comparing ligand–receptor interactions, aiding drug discovery by predicting binding affinities, and understanding structure–activity relationships, which are crucial for designing effective pharmaceuticals with desired therapeutic outcomes. The molecular IFP played a pivotal role in refining our understanding of ligand–receptor interactions. It validated the most interacting residues obtained from docking results, revealing a nuanced landscape. Notably, the counts for specific residue types were as follows: 20 for ARG (arginine), 11 for ASN (asparagine), 5 for ASP (aspartic acid), 16 for GLU (glutamic acid), 1 for GLY (glycine), 7 for ILE (isoleucine), 2 for LYS (lysine), 2 for PRO (proline), 11 for SER (serine), 5 for TRP (tryptophan), and 5 for TYR (tyrosine) (Figure 4). This detailed information on interacting residues enhances the precision of drug design efforts by highlighting key amino acids involved in crucial binding interactions. The pharmacokinetic properties of the top-ranked biflavonoids were assessed, and the results obtained are presented in Table 2. All the potential influenza NAIs violated Lipinski’s rule of 5 and did not exhibit AMES toxicity, carcinogenicity, or hepatotoxicity features. The solubility of a drug candidate that ranges between −6.5 and 0.5 is acceptable in drug discovery and design [38]. The assessment showed that all the chemical compounds possess similar solubility potential with values ranging from −2.895 to −2.974, compared to zanamivir (−2.892) and oseltamivir (−2.029). Also, an acceptable value for a drug candidate’s human intestinal absorption property is greater than 30. In this study, all the secondary metabolites possess good human intestinal absorption properties with values ranging from 76.411 to 99.200 compared to zanamivir (3.951) and oseltamivir (79.326). Furthermore, the bioavailability property of the top-ranked secondary metabolites was compared with that of zanamivir and oseltamivir. All the hit biflavonoids elicited the same bioavailability value of 0.55, while zanamivir gave 0.17 and oseltamivir gave 0.55.

Figure 4 Showing the molecular IFPs of the docked poses of each compound.
Figure 4

Showing the molecular IFPs of the docked poses of each compound.

Table 2

Pharmacokinetic properties of top-ranked biflavonoids

Ligands Lipinski violation Solubility Human intestinal absorption Hepatotoxicity Carcinogenicity Bioavailability score
Lophirone L 1 −2.93 86.135 − − 0.55
Delicaflavone 1 −2.908 81.282 − − 0.55
Lanaroflavone 1 −2.93 76.411 − − 0.55
Pulvinatabiflavone 1 −2.97 99.2 − − 0.55
Ochnaflavone 1 −2.974 90.304 − − 0.55
Zanamivir 0 −2.892 3.951 − − 0.17
Oseltamivir 0 −2.029 79.326 − − 0.55

3.3 Frontier molecular orbital properties of the top-ranked secondary metabolites

The structures of lophirone L, delicaflavone, lanaroflavone, pulvinatabiflavone, and ochnaflavone were optimized, as shown in Figure 5. The energy of the highest occupied molecular orbital (E HOMO) of a secondary metabolite indicates its ability to act as an electron donor, while the energy of the lowest unoccupied molecular orbital (E LUMO) helps to understand the electron accepting capacity of a secondary metabolite [39,40]. Lophirone L elicited the highest E HOMO value, indicating it as the best electron-donating molecule among the potential influenza NAIs. Also, lanaroflavone gave the lowest E LUMO value, suggesting that it is the best electron-accepting phytochemical (Table 3).

Figure 5 Showing the DFT computations-based HOMO diagram of (Aa) delicaflavone, (Ba) lanaroflavone, (Ca), lophirone, (Da) ochnaflavone, and (Ea) pulvinatabiflavone and LUMO diagram of (Ab) delicaflavone, (Bb) lanaroflavone, (Cb) lophirone, (Db) ochnaflavone, and (Eb) pulvinatabiflavone.
Figure 5

Showing the DFT computations-based HOMO diagram of (Aa) delicaflavone, (Ba) lanaroflavone, (Ca), lophirone, (Da) ochnaflavone, and (Ea) pulvinatabiflavone and LUMO diagram of (Ab) delicaflavone, (Bb) lanaroflavone, (Cb) lophirone, (Db) ochnaflavone, and (Eb) pulvinatabiflavone.

Table 3

Calculated frontier molecular orbital properties of selected biflavonoids

Ligands E HOMO (eV) E LUMO (eV) ΔE gap (eV) µ (eV) χ (eV) ω (eV)
Lophirone L −5.72 −1.90 3.89 3.81 3.80 −3.81
Delicaflavone −5.89 −1.89 4.00 3.89 3.78 −3.89
Lanaroflavone −5.91 −2.25 3.66 4.08 4.54 −4.08
Pulvinatabiflavone −5.86 −1.76 3.89 3.91 3.53 −3.91
Ochnaflavone −6.01 −2.02 3.99 4.02 4.05 −4.02

ΔE gap = energy gap; µ = chemical potential; χ = electronegativity; ω = electrophilicity index.

A secondary metabolite’s energy gap (ΔE gap) provides relevant information about its pharmacological potential, chemical reactivity, and stability [41]. In this study, the stability of the secondary metabolites is in the order of delicaflavone > ochnaflavone > pulvinatabiflavone > lophirone L > lanaroflavone. Also, lanaroflavone was ranked as the secondary metabolite with the best reactivity potential, and other top-ranked secondary metabolites are in the order of lophirone L > pulvinatabiflavone > ochnaflavone > delicaflavone.

Electronegativity is an essential property that helps understand secondary metabolites’ electron acceptability potential [42]. It also gives an idea of the bioactive potentials of the chemical compound. A high electron acceptability of a secondary metabolite signifies its high calculated electronegativity value [43]. Lophirone L gave the highest electronegativity value, indicating that the secondary metabolites exhibit good electron-accepting properties. Also, the electrophilicity index of secondary metabolites elucidates their pharmacological potential and potency against different diseases. A higher electrophilicity index value corresponds to a stronger electrophilic property [26]. The electrophilicity of the secondary metabolites is in the order of lanaroflavone > ochnaflavone > lophirone L > delicaflavone > pulvinatabiflavone. The frontier molecular orbital properties of selected influenza NAIs are presented in Table 3.

3.4 Molecular dynamic simulation analysis

Molecular dynamic simulation was performed on the protein-ligand complexes of the potential influenza NAIs previously identified in the molecular docking studies to understand their stability, binding mode, and interactions. The RMSD plot of the 3TI5-isophorone L complex showed that stability was attained from 0 to 14 ns, while consistent deviation was observed from 15 to 100 ns. The influenza NA’s root mean square fluctuation (RMSF) plot swung between 0.4 and 2.7 Å (Figure 6). The contact plot analysis showed that good water bridge interactions were formed with Arg118, Ile149, Lys150, Asp151, Arg152, Ser153, Tyr155, Arg156, Trp178, Gly196, Ser270, Glu276, and Asn344, while hydrophobic interaction was observed with Arg156. Also, hydrogen bond interaction was observed between lophirone L and Asp151, Arg152, Glu276, and Asn344 (Figure 6). The RMSD plot of the 3TI5-delicaflavone complex showed that stability was obtained from 0 to 56 ns, while slight deviation was observed between 57 and 62 ns and became stable from 63 to 78 ns. However, consistent deviation was observed from 79 to 100 ns (Figure 6). Also, the RMSF plot showed that the protein swung between 0.4 and 3.2 Å throughout the 100 ns simulation period. The interaction analysis showed that Asn88, Arg118, Lys150, Asp151, Arg152, Asn234, Lys264, Glu276, Glu286, Arg292, Ala346, and Ser370 formed water bridge with delicaflavone. Also, hydrogen bond interactions between the hit biflavonoid and Lys150, Asp151, Glu276, and Ala346 were observed. However, no hydrophobic interaction was observed between the ligand and influenza NA (Figure 7). The analysis of the RMSD plot of 3TI5-lanaroflavone showed that the ligand was stable at the binding pocket of influenza NA between 5 and 58 ns, while slight deviation was observed between 59 and 61 and attained stability from 62 to 100 ns. The RMSF plot of the protein oscillated between 0.5 and 3.5 Å (Figure 6). The interactions obtained from the contact plot showed that good water bridge interaction formed between Glu119, Lys150, Asp151, Arg152, Ser153, Arg156, Trp178, Asn221, Glu227, Ser246, Asn247, Glu277, Asn294, and Asn347. Also, hydrogen bond interactions were identified between Ser153, Ser247, Glu277, and Asn294 (Figure 7). The RMSD plot of 3TI5-pulvinatabiflavone showed that the hit biflavonoid was stable with a slight deviation from 0 to 79 ns, followed by a deviation between 80 and 95 ns and stability from 96 to 100 ns (Figure 6). The RMSF plot showed that the protein oscillated between 0.4 and 2.4 Å throughout the 100 ns simulation period (Figure 6). The interaction analysis performed on the contact plot of the simulated 3TI5-pulvinatabiflavone showed that water bridge interaction was observed between the ligand and Arg152, Glu277, Arg292, and Arg371, while hydrogen bond interactions were observed with Tyr178 and Glu227 (Figure 7). The 3TI5-ochnaflavone RMSD plot showed stability between 0 and 19 ns, followed by slight fluctuations between 20 and 39 ns. The complex became stable with slight fluctuation from 40 to 86 ns, followed by consistent deviation from 87 to 100 ns (Figure 6). The RMSF plot showed that the protein oscillated between 0.4 and 2.7 Å (Figure 6). The contact plot analysis showed that water bridge interactions were established between Glu119, Asp151, Arg152, Trp178, Glu277, Arg292, Asn294, Asn347, Arg371, and Arg430. Furthermore, hydrogen bond interactions between Arg118, Arg152, Tyr178, Glu277, Asn294, Asn325, Asn347, and Arg371 were observed (Figure 7).

Figure 6 Showing the RMSD of 3TI5 (blue-Cα, green backbone) in complex with (Aa) delicaflavone, (Ba) lanaroflavone, (Ca) lophirone, and (Da) ochnaflavone, (Ea) pulvinatabiflavone in red color. The RMSF of 3TI5 (blue-Cα, green backbone) in complex with (Ab) delicaflavone, (Bb) lanaroflavone, (Cb) lophirone, (Db) ochnaflavone, and (Eb) pulvinatabiflavone where the interaction of the protein with ligand residues is shown in green lines.
Figure 6

Showing the RMSD of 3TI5 (blue-Cα, green backbone) in complex with (Aa) delicaflavone, (Ba) lanaroflavone, (Ca) lophirone, and (Da) ochnaflavone, (Ea) pulvinatabiflavone in red color. The RMSF of 3TI5 (blue-Cα, green backbone) in complex with (Ab) delicaflavone, (Bb) lanaroflavone, (Cb) lophirone, (Db) ochnaflavone, and (Eb) pulvinatabiflavone where the interaction of the protein with ligand residues is shown in green lines.

Figure 7 Showing the simulation interaction diagram of 3TI5 in complex with (a) delicaflavone, (b) lanaroflavone, (c) lophirone L, (d) ochnaflavone, and (e) pulvinatabiflavone where we have shown the interactions and histogram for the count of interactions.
Figure 7

Showing the simulation interaction diagram of 3TI5 in complex with (a) delicaflavone, (b) lanaroflavone, (c) lophirone L, (d) ochnaflavone, and (e) pulvinatabiflavone where we have shown the interactions and histogram for the count of interactions.

4 Discussion

Influenza is a communicable acute respiratory infection caused by the influenza virus in humans. This infection presents with various episodes of nose, throat, and lung problems and can sometimes lead to death when left untreated [3,44]. The influenza NA enzyme breaks sialic acid groups from cell glycoproteins, releasing the virus from host cells [45]. It facilitates the binding of viruses to the sialic acid groups of cell glycoproteins, which enhances the role of HA in binding receptors, improving the enzyme activities of NA, and facilitating virus infection in their respective hosts [46,47,48]. Hence, inhibiting the enzyme can drastically reduce or eradicate the replication of the virus. Biflavonoids are naturally occurring polyphenolic compounds that display huge varieties of pharmacological activities, including antiviral, hepatoprotective, anticancer, and anti-inflammatory [15,17]. Though there are two forms of biflavonoids, the C–O–C type biflavonoids are known for some attractive therapeutic potentials due to the combination of two flavonoid moieties [15]. Drug discovery and design through computational methods have been identified as faster, cheaper, and efficient alternatives, especially when there is an urgent need for a new therapeutic arsenal to treat or manage the outbreak of an ailment [26]. In this study, molecular docking studies identified lophirone L, delicaflavone, lanaroflavone, pulvinatabiflavone, and ochnaflavone as the potential influenza NAIs with good binding affinities compared to zanamivir. All the hit molecules established good hydrogen bonds and hydrophobic, pi, and electrostatic interactions with the amino acid residues at the active site of influenza NA. These interactions contribute to the good binding affinity, inhibitory potential, and stability elicited by the hit C–O–C type biflavonoids against the influenza NA enzyme.

The molecular dynamics simulation studies showed that most of the hit biflavonoids selected attained stability with slight fluctuations observed throughout the 100 ns simulation period. The RMSD and RMSF plots of protein–ligand complexes provide relevant information on the stability of the ligand at the protein’s binding pocket and the dynamic behavior of the phytochemical with the influenza NA enzyme throughout the 100 ns simulation period [26]. In terms of stability, the ligands were reasonably stable throughout the simulation period, indicating that they can effectively inhibit influenza NA.

The contact plot of the protein–ligand complexes showed that the hit C–O–C biflavonoids formed important water bridges, hydrogen bonds, and hydrophobic interactions, which are incredibly relevant to their drug candidacy. Hydrogen bonds are crucial in protein–ligand binding, absorption, and metabolism of drug candidates. These phytochemicals’ ability to establish hydrogen bonds in the simulated system showed that they may quickly be metabolized when taken into the biological system to treat the influenza virus. Furthermore, the hydrogen bond formation with the influenza NA residues may have resulted from the abundance of hydroxyl and carbonyl groups on the biflavonoids. The huge water bridge formation between the hit biflavonoids and the enzyme showed that they could efficiently metabolize and interact extensively with the amino acid residues at the enzyme’s binding site.

The pharmacokinetic prediction assessed the hit secondary metabolites’ solubility, human intestinal absorption, bioavailability, hepatotoxicity, and carcinogenicity properties. All the chemical compounds that demonstrated good inhibitory potential against influenza NA exhibit good solubility and human intestinal absorption properties similar to oseltamivir and better than zanamivir. The top-ranked inhibitors showed a good bioavailability score compared to zanamivir and were considered non-carcinogenic compounds and non-toxic to the liver. Also, the frontier molecular orbital properties of the hit secondary metabolites showed that they exhibit good pharmacological properties.

Several studies have identified the C–O–C biflavonoids as good antiviral, antibacterial and antimicrobial agents [15]. The hit biflavonoids comprise two flavonoid units mainly dominated by luteolin and apigenin moieties. Several reports have established the excellent efficacy of the flavonoid units as potent antiviral agents [27,49,50,51]. Vacca et al. [52] evaluated some selected flavonoids’ in silico NAI properties and ranked apigenin as one of the hit molecules with a binding affinity lower than those obtained for the C–O–C biflavonoids. Hence, the presence of two flavonoid units in the potential influenza NAIs identified in this study may have contributed to their high binding affinities, such that they have a higher possibility of working synergistically with each other.

5 Conclusion

The study examined the influenza NAI potential of naturally occurring C–O–C biflavonoids. A molecular docking study was conducted to select potential drug candidates against the target receptor. Lophirone L, delicaflavone, lanaroflavone, pulvinatabiflavone, and ochnaflavone were identified as new therapeutic agents that may effectively inhibit the enzyme’s actions in normal subjects. The naturally occurring biflavonoids formed important hydrogen bonds, water bridges, and hydrophobic interactions with the amino acid residues of the enzyme throughout the 100 ns simulation period. Also, the DFT, RMSD, and RMSF plots showed that all the selected hit molecules were reasonably stable in the enzyme’s binding pocket. Additionally, the biflavonoids showed good bioavailability and pharmacokinetic properties compared to the reference drugs. Also, the density functional theory calculations identified the biflavonoids as potential inhibitors against influenza NA. The inhibitory potential of the selected biflavonoids can be further substantiated through in vitro and in vivo pharmacological studies.

# These authors are equally contributed.

Acknowledgment

The authors gratefully acknowledge the Researchers Supporting Project (grant no. RSPD2024R885), King Saud University (Riyadh, Saudi Arabia) for supporting this work.

  1. Funding information: No fund was received for the study.

  2. Author contributions: Kolade O. Faloye: writing – review and editing, writing – original draft, visualization, validation, methodology, supervision, investigation, data curation, conceptualization. Shaban Ahmad: writing – review and editing, writing – original draft, visualization, validation, methodology, supervision, investigation, data curation. Olubunmi T. Oyasowo: investigation, writing – original draft. Esther O. Shalom: writing – original draft, investigation. Nagmi Bano: methodology, investigation. Esther A. Olanudun: investigation, writing – review and editing. Tawakalit O. Kelani: investigation, writing – review and editing. Habeeb. O. Aliyu: methodology. Khalid Raza: supervision, investigation, methodology, writing – review and editing. Boluwaji O. Makinde: methodology, writing – review and editing.

  3. Conflict of interest: The authors declare that they have no known competing interest.

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

  5. Data availability statement: All data generated or analyzed during this study are included in this published article and its supplementary information file.

References

[1] Wiley CA. Emergent viral infections of the CNS. J Neuropathol Exp Neurol. 2020;79(8):823–42.10.1093/jnen/nlaa054Search in Google Scholar PubMed

[2] Hu Q, Liang W, Yi Q, Zheng Y, Wang W, Wu Y. Risk factors for death associated with severe influenza in children and the impact of the COVID-19 pandemic on clinical characteristics. Front Pediatrics. 2023;11:1–10.10.3389/fped.2023.1249058Search in Google Scholar PubMed PubMed Central

[3] Zang Y, Hao D, Wang H, Yang Z, Liu H, Zhang S. Structure-based methoxyflavone derivatives with potent inhibitory activity against various influenza neuraminidases. J Biomol Struct Dyn. 2020;38(15):4617–24.10.1080/07391102.2019.1680436Search in Google Scholar PubMed

[4] Byrd-Leotis L, Cummings RD, Steinhauer DA. The interplay between the host receptor and influenza virus hemagglutinin and neuraminidase. Int J Mol Sci. 2017;18(7):1541.10.3390/ijms18071541Search in Google Scholar PubMed PubMed Central

[5] Guo H, Rabouw H, Slomp A, Dai M, van der Vegt F, van Lent JW, et al. Kinetic analysis of the influenza A virus HA/NA balance reveals contribution of NA to virus-receptor binding and NA-dependent rolling on receptor-containing surfaces. PLoS Pathog. 2018;14(8):e1007233.10.1371/journal.ppat.1007233Search in Google Scholar PubMed PubMed Central

[6] Lowe C. Viral clouds: becoming H5N1 in Indonesia. Cult Anthropol. 2010;25(4):625–49.10.1111/j.1548-1360.2010.01072.xSearch in Google Scholar

[7] Magano J. Synthetic approaches to the neuraminidase inhibitors zanamivir (Relenza) and oseltamivir phosphate (Tamiflu) for the treatment of influenza. Chem Rev. 2009;109(9):4398–438.10.1021/cr800449mSearch in Google Scholar PubMed

[8] Shie JJ, Fang JM. Phosphonate Congeners of Oseltamivir and Zanamivir as Effective Anti‐influenza Drugs: Design, Synthesis and Biological Activity. J Chin Chem Soc. 2014;61(1):127–41.10.1002/jccs.201300544Search in Google Scholar

[9] Wang K, Zhang H, Tian Y. The current strategies of optimisation of oseltamivir against mutant neuraminidases of influenza A: a review. Eur J Med Chem. 2022;243:114711.10.1016/j.ejmech.2022.114711Search in Google Scholar PubMed

[10] Beigel JH, Hayden FG. Influenza therapeutics in clinical practice – challenges and recent advances. Cold Spring Harb Perspect Med. 2021;11(4):1–28.10.1101/cshperspect.a038463Search in Google Scholar PubMed PubMed Central

[11] Lin LT, Hsu WC, Lin CC. Antiviral natural products and herbal medicines. J Tradit Complementary Med. 2014;4(1):24–35.10.4103/2225-4110.124335Search in Google Scholar PubMed PubMed Central

[12] Musarra-Pizzo M, Pennisi R, Ben-Amor I, Mandalari G, Sciortino MT. Antiviral activity exerted by natural products against human viruses. Viruses. 2021;13(5):828.10.3390/v13050828Search in Google Scholar PubMed PubMed Central

[13] Najmi A, Javed SA, Al Bratty M, Alhazmi HA. Modern approaches in the discovery and development of plant-based natural products and their analogues as potential therapeutic agents. Molecules. 2022;27(2):349.10.3390/molecules27020349Search in Google Scholar PubMed PubMed Central

[14] Gontijo VS, Dos Santos MH, Viegas Jr C. Biological and chemical aspects of natural biflavonoids from plants: a brief review. Mini Rev Med Chem. 2017;17(10):834–62.10.2174/1389557517666161104130026Search in Google Scholar PubMed

[15] Goossens JF, Goossens L, Bailly C. Hinokiflavone and related C–O–C-type biflavonoids as anticancer compounds: properties and mechanism of action. Nat Products Bioprospect. 2021;11:365–77.10.1007/s13659-021-00298-wSearch in Google Scholar PubMed PubMed Central

[16] Mead JR, McNair N. Antiparasitic activity of flavonoids and isoflavones against Cryptosporidium parvum and Encephalitozoon intestinalis. FEMS Microbiol Lett. 2006;259(1):153–7.10.1111/j.1574-6968.2006.00263.xSearch in Google Scholar PubMed

[17] Shim SY, Lee SG, Lee M. Biflavonoids isolated from Selaginella tamariscina and their anti-inflammatory activities via ERK 1/2 signaling. Molecules. 2018;23(4):926.10.3390/molecules23040926Search in Google Scholar PubMed PubMed Central

[18] Huang W, Liu C, Liu F, Liu Z, Lai G, Yi J. Hinokiflavone induces apoptosis and inhibits migration of breast cancer cells via EMT signalling pathway. Cell Biochem Funct. 2020;38(3):249–56.10.1002/cbf.3443Search in Google Scholar PubMed PubMed Central

[19] Lin YM, Anderson M, Flavin MT, Pai YHS, Mata-Greenwood E, Pengsuparp T, et al. In vitro anti-HIV activity of biflavonoids isolated from Rhus succedanea and Garcinia multiflora. J Nat Products. 1997;60(9):884–8.10.1021/np9700275Search in Google Scholar PubMed

[20] Weniger B, Vonthron-Sénécheau C, Arango GJ, Kaiser M, Brun R, Anton R. A bioactive biflavonoid from Campnosperma panamense. Fitoterapia. 2004;75(7–8):764–7.10.1016/j.fitote.2004.09.015Search in Google Scholar PubMed

[21] AETih AE, Ghogomu RT, Sondengam BL, Caux C, Bodo B. Minor Biflavonoids from Lophira a lata Leaves. J Nat products. 2006;69(8):1206–8.10.1021/np050169wSearch in Google Scholar PubMed

[22] Zhang GG, Jing Y, Zhang HM, Ma EL, Guan J, Xue FN, et al. Isolation and cytotoxic activity of selaginellin derivatives and biflavonoids from Selaginella tamariscina. Planta Medica. 2012;78(4):390–2.10.1055/s-0031-1298175Search in Google Scholar PubMed

[23] Šamec D, Karalija E, Dahija S, Hassan ST. Biflavonoids: Important contributions to the health benefits of Ginkgo (Ginkgo biloba L.). Plants. 2022;11(10):1381.10.3390/plants11101381Search in Google Scholar PubMed PubMed Central

[24] Owoseeni OD, Patil RB, Phage PM, Ogboye RM, Ayoola MD, Famuyiwa SO, et al. Computational assessment of xanthones from African medicinal plants as aldose reductase inhibitors. Computation. 2022;10(9):146.10.3390/computation10090146Search in Google Scholar

[25] Faloye KO, Tripathi MK, Adesida SA, Oguntimehin SA, Oyetunde YM, et al. Antimalarial potential, LC–MS secondary metabolite profiling and computational studies of Zingiber officinale. J Biomol Struct Dyn. 2024;42(5):2570–85.10.1080/07391102.2023.2205949Search in Google Scholar PubMed

[26] Famuyiwa SO, Ahmad S, Fakola EG, Olusola AJ, Adesida SA, Obagunle FO, et al. Comprehensive computational studies of naturally occurring kuguacins as antidiabetic agents by targeting visfatin. Chem Afr. 2023;6:1–13.10.1007/s42250-023-00604-8Search in Google Scholar

[27] Badshah SL, Faisal S, Muhammad A, Poulson BG, Emwas AH, Jaremko M. Antiviral activities of flavonoids. Biomed Pharmacother. 2021;140:111596.10.1016/j.biopha.2021.111596Search in Google Scholar PubMed PubMed Central

[28] Lalani S, Poh CL. Flavonoids as antiviral agents for Enterovirus A71 (EV-A71). Viruses. 2020;12(2):184.10.3390/v12020184Search in Google Scholar PubMed PubMed Central

[29] Vavricka CJ, Li Q, Wu Y, Qi J, Wang M, Liu Y, et al. Structural and functional analysis of laninamivir and its octanoate prodrug reveals group specific mechanisms for influenza NA inhibition. PLoS Pathog. 2011;7(10):e1002249.10.1371/journal.ppat.1002249Search in Google Scholar PubMed PubMed Central

[30] Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010;31(2):455–61.10.1002/jcc.21334Search in Google Scholar PubMed PubMed Central

[31] Ahmad S, Sayeed S, Bano N, Sheikh K, Raza K. In-silico analysis reveals Quinic acid as a multitargeted inhibitor against Cervical Cancer. J Biomol Struct Dyn. 2023;41(19):9770–86.10.1080/07391102.2022.2146202Search in Google Scholar PubMed

[32] Alzamami A, Alturki NA, Alghamdi YS, Ahmad S, Alshamrani S, Asiri SA, et al. Hemi-Babim and fenoterol as potential inhibitors of MPro and papain-like protease against SARS-CoV-2: an in-silico study. Medicina. 2022;58(4):515.10.3390/medicina58040515Search in Google Scholar PubMed PubMed Central

[33] Yadav MK, Ahmad S, Raza K, Kumar S, Eswaran M, Pasha Km M. Predictive modeling and therapeutic repurposing of natural compounds against the receptor-binding domain of SARS-CoV-2. J Biomol Struct Dyn. 2023;41(5):1527–39.10.1080/07391102.2021.2021993Search in Google Scholar PubMed

[34] Becke AD. A new mixing of Hartree–Fock and local densityfunctional theories. J Chem Phys. 1993;98(2):137.10.1063/1.464304Search in Google Scholar

[35] Schrödinger Release 2023–1: Maestro, Schrödinger, LLC, New York, NY, 2021.Search in Google Scholar

[36] Ahmad S, Raza K. Identification of 5-nitroindazole as a multitargeted inhibitor for CDK and transferase kinase in lung cancer: a multisampling algorithm-based structural study. Mol Diversity. 2023;12(6):1–14.10.1007/s11030-023-10648-0Search in Google Scholar PubMed

[37] Ahmad S, Singh V, Gautam HK, Raza K. Multisampling-based docking reveals Imidazolidinyl urea as a multitargeted inhibitor for lung cancer: an optimisation followed multi-simulation and in-vitro study. J Biomol Struct Dyn. 2023;42(5):1–18.10.1080/07391102.2023.2209673Search in Google Scholar PubMed

[38] Ogboye RM, Patil RB, Famuyiwa SO, Faloye KO. Novel α-amylase and α-glucosidase inhibitors from selected Nigerian antidiabetic plants: an in silico approach. J Biomol Struct Dyn. 2022;40(14):6340–9.10.1080/07391102.2021.1883480Search in Google Scholar PubMed

[39] Subramanian N, Sundaraganesan N, Jayabharathi J. Molecular structure, spectroscopic (FT-IR, FT-Raman, NMR, UV) studies and first-order molecular hyperpolarizabilities of 1, 2-bis (3-methoxy-4-hydroxybenzylidene) hydrazine by density functional method. Spectrochim Acta Part A: Mol Biomol Spectrosc. 2010;76(2):259–69.10.1016/j.saa.2010.03.033Search in Google Scholar PubMed

[40] Stefaniu A, Pintilie L. Molecular descriptors and properties of organic molecules. Symmetry (group theory) and mathematical treatment in chemistry. InTech, Rijeka; 2018. p. 161–76.10.5772/intechopen.72840Search in Google Scholar

[41] Ayeni AO, Akinyele OF, Hosten EC, Fakola EG, Olalere JT, Egharevba GO, et al. Synthesis, crystal structure, experimental and theoretical studies of corrosion inhibition of 2-((4-(2-hydroxy-4-methylbenzyl) piperazin-1-yl) methyl)-5-methylphenol–A Mannich base. J Mol Structure. 2020;1219:128539.10.1016/j.molstruc.2020.128539Search in Google Scholar

[42] Srivastava K, Shimpi MR, Srivastava A, Tandon P, Sinha K, Velaga SP. Vibrational analysis and chemical activity of paracetamol–oxalic acid cocrystal based on monomer and dimer calculations: DFT and AIM approach. RSC Adv. 2016;6(12):10024–37.10.1039/C5RA24402ASearch in Google Scholar

[43] Domingo LR, Ríos-Gutiérrez M, Pérez P. Applications of the conceptual density functional theory indices to organic chemistry reactivity. Molecules. 2016;21(6):748.10.3390/molecules21060748Search in Google Scholar PubMed PubMed Central

[44] Sarukhanyan E, Shanmugam TA, Dandekar T. In silico studies reveal Peramivir and Zanamivir as an optimal drug treatment even if H7N9 avian type influenza virus acquires further resistance. Molecules. 2022;27(18):5920.10.3390/molecules27185920Search in Google Scholar PubMed PubMed Central

[45] Borau MS, Stertz S. Entry of influenza A virus into host cells – Recent progress and remaining challenges. Curr OpVirology. 2021;48:23–9.10.1016/j.coviro.2021.03.001Search in Google Scholar PubMed

[46] Matrosovich M, Herrler G, Klenk HD. Sialic acid receptors of viruses. Sialoglyco Chem Biol II: Tools Tech Identify Capture Sialoglycans. 2015;32:1–28.10.1007/128_2013_466Search in Google Scholar PubMed PubMed Central

[47] McAuley JL, Gilbertson BP, Trifkovic S, Brown LE, McKimm-Breschkin JL. Influenza virus neuraminidase structure and functions. Front Microbiol. 2019;10:39.10.3389/fmicb.2019.00039Search in Google Scholar PubMed PubMed Central

[48] Burzyńska P, Sobala LF, Mikołajczyk K, Jodłowska M, Jaśkiewicz E. Sialic acids as receptors for pathogens. Biomolecules. 2021;11(6):831.10.3390/biom11060831Search in Google Scholar PubMed PubMed Central

[49] Murali KS, Sivasubramanian S, Vincent S, Murugan SB, Giridaran B, Dinesh S, et al. Anti – chikungunya activity of luteolin and apigenin rich fraction from Cynodon dactylon. Asian Pac J Trop Med. 2015;8(5):352–8.10.1016/S1995-7645(14)60343-6Search in Google Scholar PubMed

[50] Fan W, Qian S, Qian P, Li X. Antiviral activity of luteolin against Japanese encephalitis virus. Virus Res. 2016;220:112–6.10.1016/j.virusres.2016.04.021Search in Google Scholar PubMed

[51] Men X, Li S, Cai X, Fu L, Shao Y, Zhu Y. Antiviral activity of luteolin against Pseudorabies virus in vitro and in vivo. Animals. 2023;13(4):761.10.3390/ani13040761Search in Google Scholar PubMed PubMed Central

[52] Vacca GM, Stocco G, Dettori ML, Pira E, Bittante G, Verma NK, et al. In silico evaluation of selected flavonoids as neuraminidase inhibitors: Hope for the discovery of anti-avian influenza virus compounds. Infrared Spectrosc. 2021;104(4):3956–69.10.3168/jds.2020-19491Search in Google Scholar PubMed

Received: 2024-04-17
Revised: 2024-05-22
Accepted: 2024-06-01
Published Online: 2024-06-26

© 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-2024-0053
Keywords for this article
influenza; influenza neuraminidase; molecular docking; molecular dynamics simulation; bioavailability
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 4.11.2025 from https://www.degruyterbrill.com/document/doi/10.1515/chem-2024-0053/html
Scroll to top button