Home Green “one-pot” fluorescent bis-indolizine synthesis with whole-cell plant biocatalysis
Article Open Access

Green “one-pot” fluorescent bis-indolizine synthesis with whole-cell plant biocatalysis

  • Andreea Veronica Dediu Botezatu , Gabriela Elena Bahrim , Claudia Veronica Ungureanu , Anna Cazanevscaia Busuioc , Bianca Furdui EMAIL logo and Rodica Mihaela Dinica EMAIL logo
Published/Copyright: September 26, 2023
Download Article (PDF)
Become an author with De Gruyter Brill
Submit Manuscript Author Information
Green Processing and Synthesis
From the journal Green Processing and Synthesis Volume 12 Issue 1

Abstract

An efficient one-pot route leading to bis-indolizine symmetric compounds has been developed via a new approach from the dipyridinium heterocyclic compound, reactive halogenated derivative, and activated alkyne through biocatalysis. A set of local plants was evaluated for its catalytic potential in “one-pot” biocatalysis of these valuable fluorescent compound synthesis reactions. Most of these biocatalysts containing enzymes from the oxidoreductase class (peroxidase: 0.56–1.08 mmol purpurogallin‧g−1 fresh weight‧min−1, polyphenol oxidase (PPO) : 27.19–48.95 PPO units‧mg tissue−1, CAT: 3.27–21.71 µmol O2‧g−1 fresh weight‧min−1), were used as green catalysts in the multi-component cycloaddition reaction, in an aqueous buffer solution, for the production of bis-indolizine compounds in moderate to excellent yields (45–85%). The horseradish root (Armoracia rusticana) has been selected as the most promising biocatalyst source among the evaluated plants, and the obtained yields were greater than in the conventional synthesis method. The structures of indolizine derivatives were confirmed by nuclear magnetic resonance spectra, elemental analyses, as well as Fourier transform-infrared spectra. The cytotoxicity of the latter obtained indolizine compounds on the growth of the model microorganism, Saccharomyces cerevisiae MIUG 3.6 yeast strain, was also evaluated. Various parameters (number of generations, growth rate, generation time, dry matter yield, the degree of the budding yeast cells, and the degree of yeast autolysis, fermentation intensity), which describe the yeast growth, suggest that the nutrient broth supplemented with different concentrations of bis-indolizine compounds (10 and 1 µM) had no toxic effect on the yeast strain growth, under submerged cultivation conditions.

Keywords: biocatalysis; green synthesis; enzyme; indolizine; cytotoxicity screening

1 Introduction

The synthesis of N-fused heterocycles has been a topic of research interest for over a century because this class of compounds has been found in many natural products and synthetic drugs as their basic core structure which possesses a variety of important biological activities [1,2,3]. In recent years, numerous studies have been performed to obtain molecules for pharmaceutical purposes through biocatalysis which are remarkable because of their numerous advantages such as minimizing the use of toxic solvents, reducing the reaction time, and lowering the costs [4,5,6,7]. There is a growing need to use environmentally friendly synthetic methodologies to reduce the use of toxic solvents [8]. The development of “green” concepts has determined the orientation towards new ecological methods in organic chemistry [9,10,11,12]. Biocatalysis encompasses the use of biological systems, such as whole cells from microorganisms, microalgae, or plants, or isolated enzymes, as catalytic systems in chemical synthesis [13]. Biocatalyzed reactions by enzymes from whole-cell sources, which are the frame of “green chemistry,” present many advantages such as high selectivity, mild reaction conditions, high yields, decreased reaction time, fewer steps, low toxicity, or production of ecological waste [14,15,16,17,18]. It can often be difficult to identify optimized conditions for such reactions, as several undesirable effects may occur due to the reaction conditions. Therefore, these processes require designing the synthesis route, choosing biocatalyst sources, and establishing optimal reaction conditions such as solvent, temperature, and pH [5]. The use of enzymes in synthetic transformations is steadily increasing as an alternative source of catalysis [19,20,21]. Many studies have successfully used isolated pure enzymes in organic transformations but their uses require special materials and techniques, therefore they are often expensive and not economically advantageous [14,19,22].

Various approaches have been previously reported in the literature for indolizine synthesis, including conventional multi-step synthesis of bis-indolizines from 4,4′-bispyridinium salts [23,24,25] and one-step synthesis by other methods [24,26,27,28]. The principal methods for the synthesis of indolizine compounds refer to dipolar cycloaddition reactions of pyridinium and related heteroaromatic ylides with electron-deficient alkenes or alkynes [29], C–H functionalization reactions [30], cyclization of pyridine derivatives with alkenes, alkynes or carbonyl compounds, cyclo-isomerization transformation, Scholtz reaction, and Chichibabin reaction [24,27]. An efficient and economic synthesis of 3-benzoyl indolizine was recently reported through a reaction of picolinium salts and dimethylformamide-dimethyl acetal (DMF-DMA) with triethylamine base in DMF solvent by using microwave irradiation as a “greener” method with a better yield than the conventional method [24]. Indolizine derivatives were obtained by another green method through one-pot 1,3-dipolar cycloadditions in recyclable imidazolium ionic liquids ([Omim]Br) in good yields (78–87%) and broad substrate scope [27]. Indolizines were also obtained by irradiation of 2-benzoyl-N-benzylpyridinium derivatives and dimethyl acetylene dicarboxylate [31]. A catalyst-free annulation of 2-pyridylacetates and ynals under molecular oxygen was proposed to obtain 3-acylated indolizines in very good yields (up to 91%) in toluene at 100°C [28]. Pyrrolo[2,1,5-cd]indolizine derivatives were obtained by visible-light-induced intermolecular [3 + 2] annulations with internal alkynes in very good yields (58–91%) in dimethyl sulfoxide, in the presence of rose bengal and KI at room temperature for 10 h under 20 W blue LED [32]. In 2023, a mild and metal-free synthesis of indolizines using pyridinium salts and alkenes with ambient air as a sole oxidant to catalyze [3 + 2] annulation was reported [25]. Indolizine derivatives were obtained in good yields (up to 89%) in DMSO at 100°C by treatment of homopropargyl pryidines with cesium carbonate, involving α-C–H deprotonation, 5-exo-dig cyclization, and isomerization of the exocyclic double bond [33]. Pyridinium 1,4-zwitterionic thiolate reaction with a copper carbene was reported for the synthesis of indolizine scaffolds with yields of up to 90% [34]. Although studies with less toxic syntheses of indolizine compounds or without metal catalysts are presented in the specialized literature, to our knowledge, synthesis by biocatalysis with plant enzymes in aqueous buffer solution has not been reported so far.

Several indolizine derivatives have been reported to exhibit a wide spectrum of applications in many fields such as chemistry, biology, pharmaceutical, food industries, and medicine [35,36,37]. This class of bridgehead-N-fused heterocyclic compounds demonstrated valuable biological activities [38,39,40] such as antimicrobial [41,42,43,44,45], antioxidant [35], anticancer [41], enzyme inhibition [40,46,47,48], photoluminescence [49,50], calcium-entry blocking [51,52], and anti-inflammatory [53]. These compounds are also studied as molecules of interest in material science due to their fluorescence [37,50,54,55] or electric properties [56,57]. Therefore, the development of novel and efficacious methods for the design and synthesis of indolizine derivatives is of significant concern.

In order to be able to begin the selection of a possible drug candidate, the target compounds must be low or free of toxicity. In this context, numerous studies have evaluated the cytotoxicity of natural or synthetic chemical compounds by using biological models [58,59,60]. In several studies, the yeast Saccharomyces cerevisiae is noted for its remarkable and versatile resemblance to various eukaryotic species including human cells, in cellular molecular mechanisms related to basic cellular processes, and is used as a great eukaryotic model for exploring the effects of cytotoxic compounds due to its well-featured metabolic, genetic, and morphological characteristics [61,62,63,64].

Given the considerable increase in the importance of indolizine derivatives and also the essential role of natural sources as chemical catalysts, this work aimed to obtain indolizine derivatives by an attractive route of multi-enzymatic catalysis. In this direction, the synthesis of compounds with indolizine core was obtained by a one-pot, three-component procedure through a novel route by using whole-cell plant systems (Figure 1). The main benefit of this approach is that indolizine derivatives with valuable biological properties can be obtained straightforwardly in good yields by an accessible and environmentally friendly method, under mild reaction conditions, in high yields, and in short reaction times. Moreover, this approach for the effective implementation of synthetic transformations presents significant economic and environmental impacts. The cytotoxicity of these compounds was also investigated on the Saccharomyces cerevisiae model yeast cells, during the multiplication and alcoholic fermentation processes.

Figure 1 General pathway for the biocatalyzed synthesis of indolizine derivatives (1, 2, 3) in the presence of plant enzymes in buffer solution, at room temperature.
Figure 1

General pathway for the biocatalyzed synthesis of indolizine derivatives (1, 2, 3) in the presence of plant enzymes in buffer solution, at room temperature.

2 Materials and methods

2.1 Materials

All chemicals and solvents were of analytical grade and commercially available from Merck KGaA (Merck KGaA, Darmstadt, Germany) and Fluka (Honeywell Fluka™, Fluka, Germany).

The plant materials used in this study as biocatalyst sources were horseradish roots (Armoracia rusticana), celery roots (Apium graveolens), parsnip roots (Pastinaca sativa), parsley root (Petroselinum crispum), pumpkin sprouts (Cucurbita pepo), faba bean sprouts (Vicia faba), and soy sprouts (Glycine max). All plants were purchased from local markets and farms (Galati, Romania) so that they were as fresh as possible. These are common plant varieties that can be found in local markets in Romania. The sprouts were obtained by the previously described method [26].

The yeast strain used in the study, Saccharomyces cerevisiae MIUG 3.6, was provided by the Microorganisms Collection (acronym MIUG) of the Research and Education Platform (Bioaliment) of “Dunărea de Jos” University of Galati, Romania. The pure stock cultures were maintained by cultivation on the yeast extract peptone dextrose (YPD) agar medium and preserved at 4°C.

2.2 Experimental procedures

The activities of oxidant enzymes (catalase, peroxidase, and polyphenol oxidase [PPO]) were determined for each plant sample. The enzymatic assays were performed by microspectrophotometric adapted methods.

2.2.1 Peroxidase activity assay

The determination of peroxidase (EC 1.11.1.7) activity is based on the conversion of H2O2 to H2O and O2 in the presence of a hydrogen donor (pyrogallol) and an adapted microplate assay was used [65,66,67]. Pyrogallol is oxidized to purpurogaline, a colored compound whose absorbance was measured at λ = 430 nm. To prepare the enzymatic extract, 1 g of each plant was crushed by using a commercial machine (Tefal Frutelia ZE420D38, 11, 400 W, Groupe SEB, Romania), and 5 mL of 0.1 M phosphate buffer (pH 6.5) was added. The mixture was centrifuged at 9,000 rpm, for 30 min, at 4°C, and the centrifuged supernatant was further used as a crude enzymatic extract. The test samples were obtained by mixing 25 µL of 1% H2O2, 120 µL of 50 mM pyrogallol solution, and 5 µL of the enzymatic extract. The control sample was obtained by mixing 145 µL of 50 mM pyrogallol solution with 5 µL of the enzymatic extract, while the blank consisted of the solvent mixture. The samples were incubated at 25°C for 5 min, and the reaction was stopped by adding 50 µL of 1 M H2SO4 to the reaction mixture. The change in absorbance was measured in a 96-well plate with a multiplate reader at 430 nm (iTecan Pro 200, Tecan Trading AG, Männedorf, Switzerland). The peroxidase activity was determined as mmol purpurogallin formed per gram of fresh weight per min.

2.2.2 Catalase activity assay

The determination of catalase (CAT, EC 1.11.1.6) activity was performed by an adapted microplate method [68,69]. This method is based on the measurement of the UV absorption of H2O2 degradation at λ = 240 nm. The decrease in absorbance occurs when hydrogen peroxide is degraded by catalase [70]. Enzymatic extracts were prepared by crushing 1 g of each plant with a commercial machine (Tefal Frutelia ZE420D38, 11, 400 W, Groupe SEB, Romania) and 5 mL of 67 mM phosphate buffer (pH 7.0) was added. The crude enzymatic extract was separated by centrifugation at 9,000 rpm, for 30 min at 4°C. The test sample was obtained by mixing 145 µL of 2 mM H2O2 and 5 µL of the enzyme extract. The control sample was obtained by mixing 145 µL of 0.067 M phosphate buffer (pH 7.0) with 5 µL of the enzymatic extract. The samples were analyzed in a 96-well plate with a multi-plate reader (Tecan Pro 200, Tecan Trading AG, Männedorf, Switzerland). One enzymatic unit represented the amount of enzyme needed to decrease the absorbance at λ = 240 nm by 0.05 units in 1 min, under the analyzed reaction conditions [70].

2.2.3 PPO activity assay

The determination of polyphenol-oxidase activity is based on proteins from polyphenol oxidases that catalyze the aerobic oxidation of phenolic substrates to quinones, which self-oxidizes and forms dark-brown pigments, known as melanin, which are spectrophotometrically determined at λ = 495 nm [71,72]. The enzymatic samples were prepared by mixing 1 g of plant with 5 mL of phosphate buffer (pH 6.8). After centrifugation at 9,000 rpm, for 30 min at 4°C, the supernatant was filtered through Whatman No. 1 filter paper and was further used as the crude enzymatic extract. The samples were obtained by mixing 50 µL of 0.1 M methyl catechol, 100 µL of 0.1 M phosphate buffer (pH 6.8), and 50 µL of crude enzymatic extracts. The absorbance was measured with a multi-plate reader (Tecan Pro 200, Tecan Trading AG, Männedorf, Switzerland) at 495 nm. The results were expressed as PPO units per mg of fresh weight.

2.3 Optimization of reaction conditions for whole-cell plant biocatalysis

The fresh plant materials of each selected species were washed with sterile water and crushed using a commercial blender (Tefal Frutelia ZE420D38, 11, 400 W, Groupe SEB, Romania). After that, 0.5–2 g of the plant (A. rusticana) were introduced into 25 mL sealed Erlenmeyer flasks with stoppers, containing 10 mL of phosphate buffer (pH = 6.0–8.0), and further used as whole-cell plant enzymatic systems. The preliminary optimization experiments were carried out by using the horseradish root as a biocatalyst source. The reactions were performed in 25 mL sealed Erlenmeyer flasks. The reaction mixture consisted of horseradish root enzymatic catalytic systems, 0.1 mmol dipyridinium heterocyclic compound (4,4′-dipyridyl), 0.25 mmol reactive halogenated derivative (ω-bromoacetophenone), and 0.25 mmol activated alkyne (ethyl propiolate). The reaction mixtures were continuously stirred (300 rpm) for up to 168 h. The effects of pH (6.0–8.0), the amount of plant (0.5–2.0 g), the reaction time, and temperatures (20–40°C) were monitored. The progress of each reaction was followed by thin-layer chromatography (TLC) analysis at various time intervals. The compounds were extracted and then purified from the reaction medium by extraction with chloroform and precipitated with methanol. Indolizine derivative structures and purities were verified by melting points, TLC, Fourier transform-infrared (FT-IR) spectroscopy and elemental analysis.

2.4 Indolizine “green-synthesis” reactions with whole-cell plant biocatalysts

The reaction mixture consisted of each enzymatic plant catalytic system, 0.1 mmol dipyridinium heterocyclic compound (4,4′-dipyridyl), 0.25 mmol reactive halogenated derivatives (ω-bromoacetophenone, 2-bromo-4′-methoxyacetophenone, 2-bromo-4′-nitroacetophenone), and 0.25 mmol activated alkynes (ethyl propiolate). The reaction mixtures were continuously stirred (300 rpm) at room temperature, for up to 120 h. The progress of each reaction was monitored by TLC and FT-IR analysis (Nicolet iS50, Thermo Scientific, United States) at various time intervals. For TLC analyses, the chromatography mixture was cyclohexane/ethyl acetate = 3:1 (v/v). The compounds were extracted and then purified from the reaction medium by extraction with chloroform. The results represent the average of three individual experiments.

2.5 Separation and purification of bioconversion products

Solvent extraction was used to separate the medium of the reaction and also for the separation of the reaction products. The reaction products were separated through liquid–liquid extraction with 10 mL of chloroform, three times. The organic layer was further washed with 10 mL of ultrapure water, three times, to remove any secondary products such as the intermediate bisquaternary pyridinium salts. TLC analyses were carried out for the chloroform extracts to identify the reaction products. In the next step, the chloroform layer was dried over anhydrous sodium sulfate and filtered through Whatman No.1 filter paper. The solvent was removed under reduced pressure and the crude product was purified by recrystallization in a chloroform/methanol system to finally obtain pure reaction products, respectively, bis-indolizines in good yields for whole-cell plant biocatalysis. The purity of the obtained products was analyzed by TLC, melting points, FT-IR spectroscopy, and elemental analysis using as comparative standards the bis-indolizines obtained by the conventional method [23].

2.6 Analytical methods

Melting points were determined with a Büchi Melting Point B-540. FT-IR spectra were recorded from 4,000 to 400 cm−1 with 4 cm−1 resolution on a Nicolet iS50 FT-IR spectrometer (Thermo Scientific, USA), equipped with a KBr beamsplitter, a diamond crystal, built-in ATR accessory, a DTGS detector, and Omnic Software. Elemental analysis (C, H, N) was performed with a Fisons Instruments 1108 CHNS-O elemental analyzer. Reactions were monitored by TLC using silica gel 60 UV254 Merck pre-coated silica gel plates. In TLC studies, cyclohexane/ethyl acetate = 3:1 (v/v) was used as a chromatography developing mixture. A Bruker 400 Ultrashield (400 MHz) spectrometer, operating at room temperature, was used for 1H NMR analysis and CDCl3 was used as a solvent. Abbreviations for data quoted are m, multiplet; dd, doublet of doublets; q, quartet; t, triplet; d, doublet; s, singlet (Supplementary material, S1–S3).

Diethyl 1,1′-dibenzoyl-[7,7′-bisindolizine]-3,3′-dicarboxylate (1): yellow powder, mp 273–274°C; 1H-NMR (400 MHz; CDCl3; TMS) δ/ppm: 9.99 (d, J = 7.5, 2H); 8.78 (d, J = 1.2, 2H); 7.79–7.89 [m, 6H: 4H, 2H (7.83)]; 7.43–7.74 [m, 8H: 4H, 2H, 2H (7.53, J = 7.5, J = 1.2)]; 4.42 (q, J = 7.2, 4H); 1.45 (t, J = 7.2, 6H); IR (ATR, cm−1): 3,063.43 (l, CHarom.); 2,980.91 (l, CHalif); 1,697.59 (s, C═Oester); 1,641.57 (s, C═O); 1,527.71, 1,474.86, 1,447.50, 1,426.07 (s, C═N, C═Carom); 1,340.41 (s, COester) 1,228.37, 1,179.27 (s, C–O–C); 1,077.63 (s, C–N); anal. C 73.74%; H 5.06%; N 4.73%, calcd for C36H28N2O6, C 73.96%, H 4.83%, N 4.79%.

Diethyl 1,1′-bis(4-methoxybenzoyl)-[7,7′-bisindolizine]-3,3′-dicarboxylate (2): yellow powder, mp 290–292°C; 1H-NMR (400 MHz; CDCl3; TMS) δ/ppm: 9.97 (d, J = 7.5, 2H); 8.89 (d, J = 1.2, 2H); 7.88 (d, J = 7.5, 2H); 7.70 (s, 2H); 7.30 (d, J = 8.8, 4H); 7.05 (d, J = 8.8, 4H); 4.48 (q, J = 7.2, 4H); 3.87 (s, 6H); 1.45 (t, J = 7.2, 6H); IR (ATR, cm−1): 3,118.38, 3,076.01 (l, CHarom.); 2,982.48 (l, CHalif); 1,697.24 (s, C═Oester); 1,638.65 (s, C═O); 1,596.24, 1,512.05, 1,475.58 (s, C═N, C═Carom); 1,341.30 (s, COester), 1,264.44, 1,234.54, 1,197.89 (s, C–O–C); 1,084.03 (s, C–N); anal. C 70.94%; H 4.86%; N 4.26%, calcd for C38H32N2O8, C 70.80%, H 5.00%, N 4.35%.

Diethyl 1,1′-bis(4-nitrobenzoyl)-[7,7′-bisindolizine]-3,3′-dicarboxylate (3): dark-yellow brownish powder, mp 271–273°C; 1H-NMR (400 MHz; CDCl3; TMS) δ/ppm: 10.12 (d, J = 7.5, 2H); 8.98 (d, J = 1.2, 2H); 8.01 (d, J = 8.8, 4H); 7.78 (d, J = 8.8, 4H); 7.46 (d, J = 7.5, 2H); 7.40 (s, 2H); 4.42 (q, J = 7.2, 4H); 1.45 (t, J = 7.2, 6H); IR (ATR, cm−1): 3,354.78 (l, CHarom.); 2,979.66 (l, CHalif); 1,697.86 (s, C═Oester); 1,602.25 (s, C═O); 1,443.94, 1,402.49 (s, C═N, C═Carom); 1,526.42, 1,347.14 (s, NO2); 1,224.99, 1,163.33 (s, C–O–C); 1,100 (s, C–N); anal. C 64.16%; H 4.10%; N 8.25%, calcd for C36H26N4O10, C 64.09%, H 3.88%, N 8.31%.

2.7 Cytotoxicity test: evaluation of yeast multiplication by submerged cultivation in the presence of indolizine derivatives

To determine the cytotoxicity of the indolizine derivatives, the Saccharomyces cerevisiae MIUG 3.6 yeast strain was selected as a eukaryotic cell model. The pure culture of Saccharomyces cerevisiae was reactivated on the tilted malt agar culture medium for 48 h at 25°C [73]. To obtain the inoculum, a cell suspension was made and the sizing of the inoculum was performed by direct counting using the Thoma chamber. The Saccharomyces cerevisiae yeast strain was cultivated in submerged conditions in 300 mL Erlenmeyer flasks with cotton stoppers, containing sterile YPD broth liquid medium (20 g‧L−1 peptone; 10 g‧L−1 yeast extract; 10 g‧L−1 glucose) pH = 5.5, with 20 g‧L−1 agar, supplemented with indolizine compounds at different concentrations (10−5 M, 10−6 M). After homogenization, the medium was inoculated with the inoculum (106 CFU‧mL−1). Control samples were obtained by yeast cultivation in a medium without organic compounds. The samples were incubated on an orbital shaker (Companion Comecta S.A., Spain) at 250 rpm and 25°C, for 48 h. All the experiments were done in triplicate.

The parameters evaluated to describe the yeast multiplication were the kinetic parameters that describe cell multiplication (number of generations; growth rate; generation time), dry matter yield, the degree of the budding yeast cells, and the degree of yeast autolysis [74,75] as follows:

(1) n = ( log N − log N 0 ) / log 2

where n is the number of generations, N is the number of living cells‧mL−1 after 48 h of aerobic culture with stirring, and N 0 is the number of living cells‧mL−1 after 24 h of aerobic culture with stirring.

(2) µ = n / t [ h − 1 ]

where µ is the growth rate, n is the number of generations, and t is the cultivation time.

(3) t g = 1 / µ [ h ]

where t g is the generation time.

The dry matter yield was evaluated after 48 h by placing the cultures in a stationary system for 3 days at 25°C, and the active biomass was separated by centrifugation at 6,000 rpm for 15 min at 4°C. To remove the components from the medium, the wet biomass was washed twice with sterile saline solution, when the cells were suspended in a volume of solution equal to the initial volume of the culture medium. After each wash, the cell suspension was centrifuged at 6,000 rpm for 15 min. The wet biomass thus obtained was thermobalance-dried at 105°C, resulting in a dry matter yield.

To assess the degree of budding yeast cells, wet preparations were made at 24 and 48 h, and from ten different fields, the total number of cells and the number of budded cells were determined. The average percentage of budding cells was calculated. All the experiments were done in triplicate.

The degree of autolysis was determined by mixing a suspension of cells in equal volumes with a solution of methylene blue. After 5 min, a wet microscopic preparation was performed. Autolyzed cells appeared as intensely blue-colored cells, compared to living uncolored cells. The number of living and autolyzed cells from ten different fields was determined and averages were calculated. After 48 h of cultivating under stirring conditions, the vials were kept stationary for 48 h, after which the degree of autolysis was assessed [76]. The degree of autolysis was calculated as follows:

(4) % Autolysed cells = N a / N t × 100

where N a represents the number of autolyzed cells and N t is the total number of cells.

2.8 Effect of synthesized compounds on alcoholic fermentation

For the fermentation experiment, pure yeast cultures, Saccharomyces cerevisiae, were used to evaluate the effect of the synthesized compounds on alcoholic fermentation [77]. The fermentation experiment was carried out in Erlenmeyer flasks equipped with fermentation valves, 200 mL of fermentation culture medium was introduced into each flask before inoculation, and the culture medium was supplemented with the tested compounds 1, 2, and 3 at two different concentrations (10 and 1 µM). After the installation of the fermentation valves, concentrated sulfuric acid was introduced through the upper hole, which allowed the resulting carbon dioxide to be removed during the fermentation and to retain water vapors and other volatile substances. The samples were incubated at 25°C for 4 days. At various time intervals, 24, 48, 72, and 96 h, the flasks were gently shaken to remove the formed CO2, weighed, and the amounts of CO2 released were calculated by difference [77]. The fermentation rate was assessed according to the amount of CO2 released per time unit, based on the unit volume of the medium (g of CO2 released by 1 L of medium per h). The amount of fermented sugar was calculated according to the global alcoholic fermentation reaction:

C 6 H 12 O 6 → 2CH 3 – CH 2 – OH + 2CO 2

From this balance, Z was calculated as follows:

(5) Z = Qt × 180/88 = Qt × 2 .045 g fermented sugar

The fermentation intensity, expressed as the percentage of fermented sugar that correlated to the initial amount of sugar, was calculated after a certain fermentation interval:

(6) R = Zf / Day × 100

For the fermentation experiment, the samples were incubated at 25°C for 4 days at 250 rpm. For the negative control sample preparation, there was no addition of compounds.

2.9 Statistical analysis

The data presented here represent mean ± standard deviation (SD) of three replicates. Data were subjected to statistical analysis in the Microsoft Excel program. Data were shown as mean values ± SD (n = 3).

3 Results

3.1 Extraction and characterization of enzymes (peroxidase, catalase, and PPO) from plant tissues

The greater peroxidase activity, among the analyzed plant varieties, was obtained for horseradish roots (1.08 ± 0.019 mmol purpurogallin‧g−1 fresh weight‧min−1), while the parsley roots recorded the lowest enzymatic activity of the analyzed samples (0.56 ± 0.024 mmol purpurogallin‧g−1 fresh weight‧min−1) (Figure 2a). The best catalase activities were found for horseradish and pumpkin sprouts (21.71 ± 1.3 and 18.86 ± 1.6 µmol O2‧g−1 fresh weight‧min−1). The highest PPO activity was found for pumpkin sprouts (48.95 ± 1.74). Enzymatic activities are known from the literature data to depend very much on the plant species and their cultivation conditions [71,78]. Crude plant enzymes are valuable and versatile tools for organic synthesis [14,79,80,81]. Therefore, in our study, several local plant species rich in oxidoreductase enzymes were evaluated for their ability to catalyze reactions to obtain N-heterocyclic compounds.

Figure 2 Activities of oxidoreductase enzymes: (a) peroxidase activity, (b) catalase activity, (c) PPO activity in tissue extracts for each plant species: horseradish roots (A. rusticana), celery roots (A. graveolens), parsnip roots (P. sativa), parsley roots (P. crispum), pumpkin sprouts (C. pepo), faba bean sprouts (V. faba), and soy sprouts (G. max).
Figure 2

Activities of oxidoreductase enzymes: (a) peroxidase activity, (b) catalase activity, (c) PPO activity in tissue extracts for each plant species: horseradish roots (A. rusticana), celery roots (A. graveolens), parsnip roots (P. sativa), parsley roots (P. crispum), pumpkin sprouts (C. pepo), faba bean sprouts (V. faba), and soy sprouts (G. max).

3.2 Optimization of reaction conditions for whole-cell plant biocatalysis

Aiming to optimize the synthetic yield, the influence of the biocatalytic medium and conditions were investigated (Table 1). The first experiments were performed with 1 g of horseradish roots in phosphate buffer at pH 6.0, with continuous stirring at room temperature for 168 h. By monitoring the reaction by TLC, it was found that the reactants were consumed in time and the final reaction product (compound 1) was achieved with a reaction time of more than 120 h. The reaction time was considered to be the time required to consume the 4,4′-dipyridyl reactant, meaning the hours after which its corresponding spot was no longer chromatographically identified in the reaction mixture. Further optimization experiments were made for the synthesis of compound 1, and the results are shown in Table 1. As small amounts of reactants were used in the synthesis, the increase in the plant weight made it difficult to extract the final reaction product, and therefore, these reactions resulted in smaller amounts of the desired compound. The most promising results were obtained at pH 7.0 and with 2 g of horseradish roots, when product 1 was obtained in 84% yield, at room temperature, and with a reaction time of 84 h.

Table 1

Optimization of reaction conditions for the synthesis of compound 1

Catalyst Fresh weight (g) pH of the phosphate buffer Reaction time (h)
20 ± 3°C 25 ± 3°C (room temperature) 37 ± 3°C
Horseradish roots 0.5 6.0 >120 >120 >120
0.5 7.0 >120 >120 >120
0.5 8.0 >120 >120 >120
1 6.0 >120 >120 >120
1 7.0 >120 >120 >120
1 8.0 >120 >120 >120
1.5 6.0 117 112 113
1.5 7.0 114 106 109
1.5 8.0 119 124 110
2 6.0 96 88 94
2 7.0 87 84 86
2 8.0 93 87 88

3.3 Indolizine derivative synthesis reactions with whole-cell plant biocatalysts

Further reactions were performed at room temperature (25 ± 3°C), phosphate buffer pH 7.0, 2 g of the fresh plant as the biocatalytic medium, 0.1 mmol 4,4′-dipyridyl, 0.25 mmol reactive halogenated derivatives (ω-bromoacetophenone, 2-bromo-4′-methoxyacetophenone, 2-bromo-4′-nitroacetophenone), and 0.25 mmol ethyl propiolate. Subsequently, the work was extended to the seven plants taken in this study and to the use of various substituted halogenated reactive derivatives as reactants (Figure 3). When different halogenated derivatives (ω-bromoacetophenone, 2-bromo-4′-methoxyacetophenone, 2-bromo-4′-nitroacetophenone) were used, the corresponding products were obtained with reaction times between 84 and 168 h, in moderate to very good yields (45–85%). The lowest yields were obtained for the reactions where 2-bromo-4′-nitroacetophenone was used in the biocatalyzed reactions.

Figure 3 Yields of final indolizine products: (a) 1, (b) 2, and (c) 3, achieved by using whole plant-cell systems as biocatalysts.
Figure 3

Yields of final indolizine products: (a) 1, (b) 2, and (c) 3, achieved by using whole plant-cell systems as biocatalysts.

3.4 Cytotoxic activity: evaluation of indolizine derivative toxicity on yeast multiplication by submerged cultivation

The present study sought an application of alternative approaches that present a perspective on the minimal use of animals in scientific experiments and aimed to evaluate the cytotoxicity of the compounds on Saccharomyces cerevisiae yeast cells. The values of the kinetic parameters determined in the time interval of 24–48 h, for the samples supplemented with compound 2, are the closest to those of the control sample (Table 2).

Table 2

Kinetic parameters determined after 48 h of cultivation under submerged conditions, with stirring and aeration: n – number of generations; µ – growth rate; tg – generation time

Compound Concentration n µ (h−1) tg (h)
Control 18.6 ± 0.4 0.38 ± 0.06 2.58 ± 0.26
1 1 µM 15.4 ± 0.1 0.32 ± 0.12 3.12 ± 0.28
1 10 µM 13.2 ± 0.3 0.27 ± 0.14 3.63 ± 0.14
2 1 µM 19.4 ± 0.1 0.40 ± 0.08 2.47 ± 0.36
2 10 µM 21.4 ± 0.0 0.44 ± 0.04 2.24 ± 0.28
3 1 µM 11.4 ± 0.4 0.24 ± 0.13 4.21 ± 0.16
3 10 µM 11.8 ± 0.3 0.25 ± 0.17 4.07 ± 0.24

The dry matter yield is close to the control compared to the samples to which the analyzed compounds were added: 1, 2, and 3 at concentrations of 1 and 10 µM. The best yield was obtained for the supplemented medium with compound 1 at a concentration of 10 µM, followed by the samples to which the analyzed chemical compounds were added: 1 µM compound 3 and 10 µM compound 2. A lower biomass yield compared to that of the control sample shows the samples to which compounds 2 and 3 were added at a concentration of 1 and 10 µM, respectively (Figure 4).

Figure 4 (a) Dry S. cerevisiae yeast biomass. (b) Budding degree of S. cerevisiae yeast cells, in the presence of indolizine compounds at different concentrations. The control sample was considered without the indolizine compounds in the yeast cell growth medium.
Figure 4

(a) Dry S. cerevisiae yeast biomass. (b) Budding degree of S. cerevisiae yeast cells, in the presence of indolizine compounds at different concentrations. The control sample was considered without the indolizine compounds in the yeast cell growth medium.

From Figure 5a, it can be seen that the presence of compound 1 at a concentration of 1 µM determined a lower degree of autolysis of Saccharomyces cerevisiae yeast cells in the multiplication process (2.27%, 0.87%, 1.07%) than that of the control sample after 24, 48, and 120 h of cultivation (1.60%, 2.34%, 2.68%). Also, the presence of compound 1 at a concentration of 10 µM determined a lower degree of autolysis after 24 and 48 h of cultivation (0.82%, 1.04%) than in the case of the control sample; however, after 120 h of cultivation, it can be seen that the degree of autolysis has a higher value than that of the control sample. Figure 5b shows that the presence of compound 2 in the cultivation medium of Saccharomyces cerevisiae yeast cells, at a concentration of 1 µM, determined lower values of the degree of autolysis than those presented by the control sample after 24, 48, and 120 h of cultivation. Also, the presence of compound 2 at a concentration of 10 µM in the cultivation medium, determined lower values of the degree of autolysis (1.09%, 1.36%) than those of the control sample (2.34%, 2.68%) after 48 and 120 h of cultivation. The presence of compound 3 in the growth medium, at both tested concentrations, determined higher degrees of autolysis after 24 h with approximately 0.6% than that of the control sample. From Figure 5c, it can be seen that after 48 and 120 h of cultivation, the values of the degree of autolysis for the samples supplemented with compound 3 at both tested concentrations show values very close to those presented by the control sample after 48 and 120 h of cultivation.

Figure 5 The degree of autolysis of yeast cells for the cultivation medium supplemented with compounds: (a) 1, (b) 2, and (c) 3 at different concentrations. The control sample was considered without the indolizine compound in the yeast cell growth medium.
Figure 5

The degree of autolysis of yeast cells for the cultivation medium supplemented with compounds: (a) 1, (b) 2, and (c) 3 at different concentrations. The control sample was considered without the indolizine compound in the yeast cell growth medium.

Figure 6 shows that the multiplication dynamics of yeast cells for the control sample were similar to those of the samples containing the studied compounds, meaning that these compounds do not significantly influence the behavior of yeast growth.

Figure 6 The multiplication dynamics of yeast cells for the cultivation medium supplemented with compounds: (a) 1, (b) 2, and (c) 3 at different concentrations. The control sample was considered without the indolizine compound in the yeast cell growth medium.
Figure 6

The multiplication dynamics of yeast cells for the cultivation medium supplemented with compounds: (a) 1, (b) 2, and (c) 3 at different concentrations. The control sample was considered without the indolizine compound in the yeast cell growth medium.

Regarding the effect of the synthesized compounds on alcoholic fermentation, from Figure 7a, it can be seen that the grams of CO2 released during the fermentation process, related to the volume of 1 L of the fermentative medium, shows lower values in the case of the control sample after 96 h of cultivation compared to the samples supplemented with the studied compounds. The highest amounts of CO2 are shown by compound 2, at the tested concentrations of 10 and 1 µM, followed by those of compound 1. Therefore, these results indicate that the compounds stimulate the fermentative capacity of the yeast Saccharomyces cerevisiae.

Figure 7 Fermentation (a) rate and (b) intensity of alcoholic fermentation in the presence of compounds: 1, 2, and 3 at different concentrations. The control sample was considered without the indolizine compound in the yeast cell growth medium.
Figure 7

Fermentation (a) rate and (b) intensity of alcoholic fermentation in the presence of compounds: 1, 2, and 3 at different concentrations. The control sample was considered without the indolizine compound in the yeast cell growth medium.

Figure 7b shows that the fermentation intensity of the control sample has the lowest value compared to the samples that were supplemented with the analyzed compounds: 1, 2, or 3 at concentrations of 1 and 10 µM. The sample containing compound 2 at the minimum analyzed concentration, 1 µM, has the highest value of fermentation intensity (22.77%), being approximately 3.7 times higher than that of the control. Compound 3 at the minimum analyzed concentration, 1 µM, shows a value of fermentation intensity close to that of the control. Samples containing compound 1, at both tested concentrations, also showed fermentation intensity higher values than the control sample.

4 Discussion

In recent years, the need to use environmentally friendly synthetic methodologies has emerged, especially in the chemical and pharmaceutical industries that arise from the large-scale use of solvents [3,82,83]. The use of polar aprotic solvents has become a major focus of green chemistry because of their impact on the environment and human health. The search for solvents with reduced environmental impact is one of the major goals identified in chemical synthesis [84,85]. In this research, this concern prompted the use of green solvents, such as water, to improve the safety of synthetic processes to obtain indolizine derivatives.

Seven plants were screened as enzymatic sources for the catalysis of one-pot indolizine derivatives synthesis. The initial experiments demonstrated the synthesis of the desired product in the presence of the enzymatic extract of horseradish roots. As a result, the research was expanded by testing other six local plants for reaction optimization purposes. The multi-step reaction was performed in a one-pot system by cascading biocatalysis, with multiple enzymes from whole plant tissues to obtain reaction products with good isolated yields (45–85%) to minimize the number of unwanted by-products and also to avoid the use of toxic solvents. After the separation and purification of the synthesized bis-indolizines, it was found that they have the expected structures and purities (Figure 8), the results of the present analysis being consistent with those of control bis-indolizines previously obtained by classical chemical synthesis [86]. Future studies can benefit from these results considering that this approach could easily be extended to screen larger libraries of potential biocatalysts from plant sources.

Figure 8 FT-IR analysis of compounds: (a) 1, (b) 2, and (c) 3 obtained through conventional catalysis (CS) and plant biocatalyzed reactions: HR – horseradish root, PRSNR – parsnip root, CR – celery root, FBG – faba bean sprouts, PG – pumpkin sprouts, and PRSLP – parsley root.
Figure 8

FT-IR analysis of compounds: (a) 1, (b) 2, and (c) 3 obtained through conventional catalysis (CS) and plant biocatalyzed reactions: HR – horseradish root, PRSNR – parsnip root, CR – celery root, FBG – faba bean sprouts, PG – pumpkin sprouts, and PRSLP – parsley root.

By comparing the reaction conditions in classical and biocatalyzed synthesis and the yields in final products, it was found that the use of multi-enzyme systems to catalyze the reactions to obtain bis-indolizines was the most effective among the studied methods (Table 3). The advantages of using a multi-enzyme system and the low cost compared to the use of pure enzymes, which require purification and high costs, have also been found. These whole-cell systems demonstrated essential advantages such as reducing the consumption of toxic solvents, performing multi-step reactions in “one-pot,” reducing the reaction by-products, and decreasing reaction costs [87,88]. Application of cheap and green catalysts, environmentally benign reaction conditions, and good to high yields are salient features of this method.

Table 3

Yields, melting points, and reaction conditions for the synthesis of Compounds 1–3

Compound m p (°C) Classical synthesis [86] Plant whole-cell biocatalysis (horseradish root experiments) Whole cells of Y. lipolytica biocatalysis [26]
Time (min) Yield (%) Time (h) Yield (%) Time (min) Yield (%)
1 273–274 360 58 88 85 144 77
2 236–237 180 58 84 77 144 47
3 229–230 240 56 87 45 144 48

The proposed reaction mechanism implies the formation of the pyridinium salts from pyridine derivatives and halogenated-carbonyl compounds (Figure 4). The free radical products generated by oxidases are highly reactive species that can, in some cases, covalently alter the heme group of the enzyme [80]. For example, for horseradish peroxidase (HRP), the substrates for which this type of reaction has been noted cover alkyl and aryl hydrazines, nitromethane, or cyclopropanone hydrate. Low reactivity radicals can be added to vinyl heme groups, and these changes in the prosthetic heme also occur in some cases with two-electron oxidation products formed by peroxidases when they oxidize halide and pseudohalide ions. Therefore, the oxidation of bromide by HRP results in the addition of HOBr to the vinyl groups in the enzyme heme [89]. Thus, this could explain the uptake of the bromine ion from the reaction medium and its addition in the form of HOBr to the vinyl groups in the heme oxidases. Subsequently, the pyridinium-N-ylides were generated. The Fe–N coordination between the prosthetic heme and pyridinium-N-ylides enhanced the reaction rate with the activated alkyne and showed an overall improvement in catalytic efficiency to give the corresponding dihydro-indolizines as the primary cycloadducts. Finally, by rearrangement and in situ dehydrogenation of the primary cycloadduct, the indolizine derivatives were obtained (Figure 9). The mechanism was proposed according to other studies from the literature [90,91].

Figure 9 The proposed mechanism pathway for the substrate conversion in pyridinium-ylide intermediates and further 1,3-dipolar cycloaddition to form indolizine derivatives 1, 2, and 3 with enzymatic catalysts from plant sources.
Figure 9

The proposed mechanism pathway for the substrate conversion in pyridinium-ylide intermediates and further 1,3-dipolar cycloaddition to form indolizine derivatives 1, 2, and 3 with enzymatic catalysts from plant sources.

The cytotoxicity of the studied compounds was previously tested by the Triticum test, and it was found that the presence of the compounds in the germination process of wheat seeds (Triticum aestivum) had no toxic effects [26]. This study continued to evaluate the cytotoxicity of these compounds on model microorganisms to assess the impact of compounds on the environment. In recent years, attempts have been made to reduce the number of animal tests due to the ethical issues associated with them, but also disadvantages such as high costs and the long time required to perform such experiments [92]. In this process, the direction of reduction, refining, and replacement of laboratory tests on animals was followed in many types of research, which involves the search for alternative methods and model organisms [93,94]. Yeast cells are often used as a model organism in laboratory testing of chemicals because they react to stress by triggering a response to it as well as adapting to the new environment. If the stress is too strong, it can even cause cell death [94]. Following these results, it was found that the presence of indolizine compounds in the yeast cultivation medium of Saccharomyces cerevisiae does not negatively influence the behavior of the yeast cultures by cultivation under aerobic submerged conditions, with continuous stirring. By supplementing the fermentation medium with these compounds, a stimulation of alcoholic fermentation was found for all analyzed samples compared to the control sample, where no synthetic compound was added. The maximum fermentation intensity was observed when the culture medium was supplemented with compound 2 at a concentration of 1 μM. It can be concluded that these compounds do not have negative effects on the multiplication and fermentation processes of the Saccharomyces cerevisiae yeast cells. This kind of in vivo assay on model microorganisms is valuable to pursuing various applications of synthetic and natural compounds in chemical and pharmaceutical industries [59,60,95]. The current state of research in response to cellular stress and cell death shows that although there are differences between the response pathways of yeasts and higher eukaryotes, they reinforce the idea that many aspects are phylogenetically conserved and therefore yeasts are ideal versatile models for evaluating the basic molecular pathways of these processes [61,63,96].

5 Conclusions

We have demonstrated the potential of using crude plant enzymatic extracts as biocatalysts with excellent improvements such as reduced reaction time, selectivity, increased productivity, and low costs. In this article, we report the synthesis of fluorescent indolizine compounds, recognized as powerful tools in many research fields, using a “green chemistry” method by using whole plant-cell biocatalysis, making it more attractive for industrial possible drug production. The results highlighted in this research encourage the use of reproducible and cheap techniques for application in industry to optimize drug production processes with the utilization of biocatalysts from natural sources. This multi-component reaction, which takes place under mild conditions, has provided an interesting new pathway to obtain fluorescent indolizines with reduced costs and good yields in metal-free catalytic systems. In the worldwide market for the production of a great variety of drugs, where companies try to improve their processes to reduce waste and make them more reliable in terms of environmental concerns, this might be considered a competitive process. Furthermore, the final products were evaluated for their cytotoxicity on the model microorganism Saccharomyces cerevisiae and no significant toxicity was found by evaluating the values of the kinetic parameters that describe the growth of this yeast. The present work provides potentially new avenues for the use of enzymes from plant sources in organic compound synthesis and drug development in environmentally friendly conditions.

Acknowledgement

The authors gratefully acknowledge the Erasmus KA220-HED, Cooperation Partnership, number 2022-1-TR01-KA220-HED-000089361, 7171, financed by the European Union. The authors would like to warmly acknowledge “Dunarea de Jos” University, ECEE, and MORAS infrastructure, for financial and technical support.

  1. Funding information: This work was supported by a grant from the Romanian National Authority for Scientific Research, CNCS – UEFISCDI, project number PN-II-ID-PCE-2011-3-0226.

  2. Author contributions: Andreea Veronica Dediu Botezatu: writing – original draft, methodology, formal analysis, visualization, conceptualization; Gabriela Elena Bahrim: methodology, formal analysis, resources, supervision; Claudia Veronica Ungureanu: methodology, formal analysis; Anna Cazanevscaia Busuioc: writing – original draft, formal analysis; Bianca Furdui: writing – review and editing, methodology, resources, conceptualization; Rodica Mihaela Dinica: writing – review and editing, conceptualization, methodology, visualization, resources, project administration.

  3. Conflict of interest: The authors state no conflict of interest.

  4. Data availability statement: The data used to support the findings of this study are included in the article. If further data or information are required, these are available from the corresponding author upon request.

Appendix
Figure A1 1H NMR spectrum of indolizine compound 1.
Figure A1

1H NMR spectrum of indolizine compound 1.

Figure A2 1H NMR spectrum of indolizine compound 2.
Figure A2

1H NMR spectrum of indolizine compound 2.

Figure A3 1H NMR spectrum of indolizine compound 3.
Figure A3

1H NMR spectrum of indolizine compound 3.

References

[1] Liu Y, Shao E, Zhang Z, Yang D, Li G, Cao H, et al. A novel indolizine derivative induces apoptosis through the mitochondria p53 pathway in HepG2 cells. Front Pharmacol. 2019;10:1–12. 10.3389/fphar.2019.00762.Search in Google Scholar PubMed PubMed Central

[2] Kim DW, Lee JH, Kim HY, Shin J, Kim K, Lee S, et al. Fluorescent indolizine derivative YI-13 detects amyloid-β monomers, dimers, and plaques in the brain of 5XFAD Alzheimer transgenic mouse model. PLoS One. 2020;15:1–20. 10.1371/journal.pone.0243041.Search in Google Scholar PubMed PubMed Central

[3] Zeng K, Mei R, Dechert S, Ackermann L, Zhang K. A recyclable stereoauxiliary aminocatalyzed strategy for one-pot synthesis of indolizine-2-carbaldehydes. Commun Chem. 2023;6:1–9. 10.1038/s42004-023-00828-2.Search in Google Scholar PubMed PubMed Central

[4] Sulman EM, Matveeva VG, Bronstein LM. Design of biocatalysts for efficient catalytic processes. Curr Opin Chem Eng. 2019;26:1–8. 10.1016/j.coche.2019.06.005.Search in Google Scholar

[5] Winkler CK, Schrittwieser JH, Kroutil W. Power of biocatalysis for organic synthesis. ACS Cent Sci. 2021;7:55–71. 10.1021/acscentsci.0c01496.Search in Google Scholar PubMed PubMed Central

[6] Siedentop R, Claaßen C, Rother D, Lütz S, Rosenthal K. Getting the most out of enzyme cascades: strategies to optimize in vitro multi-enzymatic reactions. Catalysts. 2021;11:1183. 10.3390/catal11101183.Search in Google Scholar

[7] Comito M, Monguzzi R, Tagliapietra S, Palmisano G, Cravotto G. Efficient pilot-scale synthesis of the key cefonicid intermediate at room temperature. Green Process Synth. 2022;11:96–105. 10.1515/gps-2022-0007.Search in Google Scholar

[8] Proença F, Costa M. A one-pot synthesis of substituted pyrido[2,3-b]indolizines. Tetrahedron. 2011;67:1071–5. 10.1016/j.tet.2010.12.047.Search in Google Scholar

[9] Begander B, Huber A, Sperl J, Sieber V. Development of a cofactor balanced, multi enzymatic cascade reaction for the simultaneous production of L-alanine and L-serine from 2-keto-3-deoxy-gluconate. Catalysts. 2020;11:31.10.3390/catal11010031Search in Google Scholar

[10] Illanes A. Enzyme biocatalysis: Principles and applications. Dordrecht: Springer Dordrecht; 2008. 10.1007/978-1-4020-8361-7.Search in Google Scholar

[11] Tabacaru A, Botezatu AVD, Horincar G, Furdui B, Dinica RM. Green accelerated synthesis, antimicrobial activity and seed germination test of quaternary ammonium salts of 1,2-bis(4-pyridyl)ethane. Molecules. 2019;24:2424. 10.3390/molecules24132424.Search in Google Scholar PubMed PubMed Central

[12] Yi D, Bayer T, Badenhorst CPS, Wu S, Doerr M, Höhne M, et al. Recent trends in biocatalysis. Chem Soc Rev. 2021;50:8003–49. 10.1039/d0cs01575j.Search in Google Scholar PubMed PubMed Central

[13] Zhao Q, Ansorge-Schumacher MB, Haag R, Wu C. Living whole-cell catalysis in compartmentalized emulsion. Bioresour Technol. 2020;295:122221. 10.1016/j.biortech.2019.122221.Search in Google Scholar PubMed

[14] Garzón-Posse F, Becerra-Figueroa L, Hernández-Arias J, Gamba-Sánchez D. Whole cells as biocatalysts in organic transformations. Molecules. 2018;23:1265. 10.3390/molecules23061265.Search in Google Scholar PubMed PubMed Central

[15] Bezborodov AM, Zagustina NA. Enzymatic biocatalysis in chemical synthesis of pharmaceuticals (Review). Appl Biochem Microbiol. 2016;52:237–49. 10.1134/S0003683816030030.Search in Google Scholar

[16] Cordell GA, Lemos TLG, Monte FJQ, De Mattos MC. Vegetables as chemical reagents. J Nat Prod. 2007;70:478–92. 10.1021/np0680634.Search in Google Scholar PubMed

[17] Vandenberghe A, Markó IE, Lucaccioni F, Lutts S. Enantioselective hydrolysis of racemic 1-phenylethyl acetate by an enzymatic system from fresh vegetables. Ind Crops Prod. 2013;42:380–5. 10.1016/j.indcrop.2012.06.003.Search in Google Scholar

[18] Khan MM, Khan S, Saigal, Sahoo SC. Efficient and eco-friendly one-pot synthesis of functionalized furan-2-one, pyrrol-2-one, and tetrahydropyridine using lemon juice as a biodegradable catalyst. ChemistrySelect. 2018;3:1371–80. 10.1002/slct.201702933.Search in Google Scholar

[19] Davis BG, Boyer V. Biocatalysis and enzymes in organic synthesis. Nat Prod Rep. 2001;18:618–40. 10.1039/b003667f.Search in Google Scholar PubMed

[20] Liu B, Qian X, Wu Q, Lin X. Two lipase-catalyzed sequential synthesis of drug derivatives in organic media. Enzyme Microb Technol. 2008;43:375–80. 10.1016/j.enzmictec.2008.05.008.Search in Google Scholar

[21] Birolli WG, Ferreira IM, Alvarenga N, Santos DdeA, de Matos IL, Comasseto JV, et al. Biocatalysis and biotransformation in Brazil: An overview. Biotechnol Adv. 2015;33:481–510. 10.1016/j.biotechadv.2015.02.001.Search in Google Scholar PubMed

[22] Hanefeld U, Hollmann F, Paul CE. Biocatalysis making waves in organic chemistry. Chem Soc Rev. 2022;51:594–627. 10.1039/d1cs00100k.Search in Google Scholar PubMed

[23] Dinica RM, Druta II, Pettinari C. The synthesis of substituted 7,7′-bis-indolizines via 1,3-dipolar cycloaddition under microwave irradiation. Synlett. 2000;7:1013–5. 10.1055/s-2000-6657.Search in Google Scholar

[24] Sumanth G, Saini SM, Lakshmikanth K, Mangubhai GS, Shivaprasad K, Chandrashekharappa S. Microwave-assisted improved regioselective synthesis of 3-benzoyl indolizine derivatives. J Mol Struct. 2023;1286:135561. 10.1016/j.molstruc.2023.135561.Search in Google Scholar

[25] Qiu D, Ni H, Su Y. Halogen bond-catalyzed oxidative annulation of N-Alkyl pyridinium salts and alkenes with air as a sole oxidant: Metal-free synthesis of indolizines. ChemistrySelect. 2023;8:e202300382. 10.1002/slct.202300382.Search in Google Scholar

[26] Botezatu (Dediu) AV, Horincar G, Ghinea IO, Furdui B, Bahrim G-EE, Barbu V, et al. Whole-cells of Yarrowia lipolytica applied in “one pot” indolizine biosynthesis. Catalysts. 2020;10:1–16. 10.3390/catal10060629.Search in Google Scholar

[27] Sroor FM, Mukhtar SS, Hafez TS, Tohamy WM, Hassaneen HM, Saleh FM. A facile and robust approach for synthesis and structural characterization of an unprecedented ring system of 4H-pyrazolo[3,4-f]indolizine-4,9(2H)-dione derivatives. Tetrahedron. 2023;134:133303. 10.1016/j.tet.2023.133303.Search in Google Scholar

[28] Chen Z, Liang P, Ma X, Luo H, Xu G, Liu T, et al. Catalyst-free annulation of 2-pyridylacetates and ynals with molecular oxygen: An access to 3-acylated indolizines. J Org Chem. 2019;84:1630–9. 10.1021/acs.joc.8b02883.Search in Google Scholar PubMed

[29] Shang Y, Zhang M, Yu S, Ju K, Wang C, He X. New route synthesis of indolizines via 1,3-dipolar cycloaddition of pyridiniums and alkynes. Tetrahedron Lett. 2009;50:6981–4. 10.1016/j.tetlet.2009.09.143.Search in Google Scholar

[30] Kahar NM, Nabar KU, Jadhav PP, Dawande SG. Rhodium(II)-Catalyzed Highly Stereoselective C3 Functionalization of Indolizines with N-Sulfonyl-1,2,3-triazoles. Asian J Org Chem. 2019;8:79–82. 10.1002/ajoc.201800631.Search in Google Scholar

[31] Dohmen C, Ihmels H, Kreienmeier R, Patrick BO. Synthesis of a crystallochromic indolizine dye by a base- and catalyst-free photochemical route. Chem Commun. 2019;55:11071–4. 10.1039/c9cc04730a.Search in Google Scholar PubMed

[32] Zhang Y, Yu Y, Liang B, Pei Y, Liu X, Yao H, et al. Synthesis of pyrrolo[2,1,5-cd]indolizine rings via visible-light-induced intermolecular [3 + 2] cycloaddition of indolizines and alkynes. J Org Chem. 2020;85:10719–27. 10.1021/acs.joc.0c01253.Search in Google Scholar PubMed

[33] Xiao K, Zhu C, Lin M, Song C, Chang J. Base-promoted cycloisomerization for the synthesis of indolizines and related heterocycles. ChemistrySelect. 2018;3:11270–2. 10.1002/slct.201802620.Search in Google Scholar

[34] Monreal-Corona R, Díaz-Jiménez À, Roglans A, Poater A, Pla-Quintana A. Indolizine synthesis through annulation of pyridinium 1,4-thiolates and copper carbenes: a predictive catalysis approach. Adv Synth Catal. 2023;365:760–6. 10.1002/adsc.202201277.Search in Google Scholar

[35] Sharma V, Kumar V. Indolizine: A biologically active moiety. Med Chem Res. 2014;23:3593–606. 10.1007/s00044-014-0940-1.Search in Google Scholar

[36] Sadowski B, Klajn J, Gryko DT. Recent advances in the synthesis of indolizines and their π-expanded analogues. Org Biomol Chem. 2016;14:7804–28. 10.1039/c6ob00985a.Search in Google Scholar PubMed

[37] Wan J, Zheng CJ, Fung MK, Liu XK, Lee CS, Zhang XH. Multifunctional electron-transporting indolizine derivatives for highly efficient blue fluorescence, orange phosphorescence host and two-color based white OLEDs. J Mater Chem. 2012;22:4502–10. 10.1039/c2jm14904d.Search in Google Scholar

[38] Singh P, Kim YJ, Zhang D, Yang DC. Biological Synthesis of Nanoparticles from Plants and Microorganisms. Trends Biotechnol. 2016;34:588–99. 10.1016/j.tibtech.2016.02.006.Search in Google Scholar PubMed

[39] Singh GS, Mmatli EE. Recent progress in synthesis and bioactivity studies of indolizines. Eur J Med Chem. 2011;46:5237–57. 10.1016/j.ejmech.2011.08.042.Search in Google Scholar PubMed

[40] Baussanne I, Firstova O, Dediu AB, Larosa C, Furdui B, Ghinea IO, et al. Interest of novel N-alkylpyridinium-indolizine hybrids in the field of Alzheimer’s disease: Synthesis, characterization and evaluation of antioxidant activity, cholinesterase inhibition, and amyloid fibrillation interference. Bioorg Chem. 2021;116:105390. 10.1016/j.bioorg.2021.105390.Search in Google Scholar PubMed

[41] Moon SH, Jung Y, Kim SH, Kim I. Synthesis, characterization and biological evaluation of anti-cancer indolizine derivatives via inhibiting β-catenin activity and activating p53. Bioorg Med Chem Lett. 2016;26:110–3. 10.1016/j.bmcl.2015.11.021.Search in Google Scholar PubMed

[42] Olejníková P, Birošová L, Švorc L, Vihonská Z, Fiedlerová M, Marchalín Š, et al. Newly synthesized indolizine derivatives - Antimicrobial and antimutagenic properties. Chem Pap. 2015;69:983–92. 10.1515/chempap-2015-0093.Search in Google Scholar

[43] Darwish ES. Facile synthesis of heterocycles via 2-picolinium bromide and antimicrobial activities of the products. Molecules. 2008;13:1066–78. 10.3390/molecules13051066.Search in Google Scholar PubMed PubMed Central

[44] Lingala S, Nerella R, Cherukupally R, Das AK. Synthesis and comparative anti-tubercular activity of indolizine derivatives of Isoniazid/Pyrazinamide/Ethionamide. Int J Pharm Sci Rev Res. 2011;6:128–31.Search in Google Scholar

[45] Furdui B, Dinica RM, Tabacaru A, Pettinari C. Synthesis and physico-chemical properties of a novel series of aromatic electron acceptors based on N-heterocycles. Tetrahedron. 2012;68:6164–8. 10.1016/j.tet.2012.05.077.Search in Google Scholar

[46] Teklu S, Gundersen LL, Larsen T, Malterud KE, Rise F. Indolizine 1-sulfonates as potent inhibitors of 15-lipoxygenase from soybeans. Bioorg Med Chem. 2005;13:3127–39. 10.1016/j.bmc.2005.02.056.Search in Google Scholar PubMed

[47] Weide T, Arve L, Prinz H, Waldmann H, Kessler H. 3-Substituted indolizine-1-carbonitrile derivatives as phosphatase inhibitors. Bioorg Med Chem Lett. 2006;16:59–63. 10.1016/j.bmcl.2005.09.051.Search in Google Scholar PubMed

[48] Ali MA, Ismail R, Choon TS, Kumar RS, Asad M, Almansour AI, et al. Alzheimer diseases: substituted spiro [2.3′] oxindolespiro [3.2″]- 5, 6-dimethoxy-indane-1″-one- indolizine analogue as inhibitors of acetylcholinesterase. Med Chem (Los Angeles). 2012;2:2–5. 10.4172/2161-0444.1000106.Search in Google Scholar

[49] Vlahovici A, Druţa I, Andrei M, Cotlet M, Dinica R. Photophysics of some indolizines, derivatives from bipyridyl, in various media. J Lumin. 1999;82:155–62. 10.1016/S0022-2313(99)00027-7.Search in Google Scholar

[50] Song YR, Lim CW, Kim TW. Synthesis and photophysical properties of 1,2-diphenylindolizine derivatives: Fluorescent blue-emitting materials for organic light-emitting device. Luminescence. 2016;31:364–71. 10.1002/bio.2968.Search in Google Scholar PubMed

[51] Gupta SP, Mathur AN, Nagappa AN, Kumar D, Kumaran S. A quantitative structure-activity relationship study on a novel class of calcium-entry blockers: 1-[{4-(Aminoalkoxy)phenyl}sulphonyl]indolizines. Eur J Med Chem. 2003;38:867–73. 10.1016/j.ejmech.2003.08.001.Search in Google Scholar PubMed

[52] Gubin J, Lucchetti J, Mahaux J, Rosseels G, Clinet M, Polster P, et al. A Novel Class of Calcium-Entry Blockers: The 1-[[4-(Aminoalkoxy)phenyl]sulfonyl]indolizines. J Med Chem. 1992;35:981–8. 10.1021/jm00084a002.Search in Google Scholar PubMed

[53] Dawood KM, Abdel-Gawad H, Rageb EA, Ellithey M, Mohamed HA. Synthesis, anticonvulsant, and anti-inflammatory evaluation of some new benzotriazole and benzofuran-based heterocycles. Bioorg Med Chem. 2006;14:3672–80. 10.1016/j.bmc.2006.01.033.Search in Google Scholar PubMed

[54] Delcamp JH, Yella A, Holcombe TW, Nazeeruddin MK, Grätzel M. The molecular engineering of organic sensitizers for solar-cell applications. Angew Chemie Int Ed. 2013;52:376–80. 10.1002/anie.201205007.Search in Google Scholar PubMed

[55] Dinică R, Furdui B, Bahrim G, Demeunynck M. Précurseurs de nouveaux hétérocycles D â€TM intéret biologique. Rev Roum Chim. 2008;53:21–4.Search in Google Scholar

[56] Leontie L, Druta I, Furdui B, Rusu GI. On the mechanism of electrical conduction in some new quaternary salts of bipyridine and indolizine pyridine in thin films. Prog Org Coat. 2007;58:303–11. 10.1016/j.porgcoat.2007.01.003.Search in Google Scholar

[57] Furdui B, Dinicǎ R, Demeunynck M, Druţǎ I, Vlahovici A. New reactive pyridinium-indolizines fluorophores. Rev Roum Chim. 2007;52:633–7.10.1002/chin.200816162Search in Google Scholar

[58] Chinna Rajesh U, Purohit G, Rawat DS. One-pot synthesis of aminoindolizines and chalcones using CuI/CSP nanocomposites with anomalous selectivity under green conditions. ACS Sustain Chem Eng. 2015;3:2397–404. 10.1021/acssuschemeng.5b00701.Search in Google Scholar

[59] Ruiz-Gómez MJ, Martínez-Morillo M. Iron(III) chloride hexahydrate does not enhance methotrexate cytotoxicity on Saccharomyces cerevisiae. Chemotherapy. 2006;52:226–30. 10.1159/000094768.Search in Google Scholar PubMed

[60] Bjornsti MA, Knab AM, Benedetti P. Yeast Saccharomyces cerevisiae as a model system to study the cytotoxic activity of the antitumor drug camptothecin. Cancer Chemother Pharmacol. 1994;34:27–30. 10.1007/BF00684856.Search in Google Scholar PubMed

[61] Moriya H. The expression level and cytotoxicity of green fluorescent protein are modulated by an additional N-terminal sequence. AIMS Biophys. 2020;7:121–32. 10.3934/BIOPHY.2020010.Search in Google Scholar

[62] Microcystin-lr C, Vasconcelos VM, Campos A. New Insights in Saccharomyces cerevisiae Response Proteomics and Gene Expression. Toxins (Basel). 2020;12(10):667. 10.3390/toxins12100667.Search in Google Scholar PubMed PubMed Central

[63] Sudharshan SJ, Tirupathi R, Dyavaiah M. Astaxanthin reduces perfluorooctanoic acid cytotoxicity in Saccharomyces cerevisiae. Toxicol Res (Camb). 2019;8:1009–15. 10.1039/c9tx00215d.Search in Google Scholar PubMed PubMed Central

[64] Dymond JS. Saccharomyces cerevisiae Growth Media. Vol. 533. 1st edn. London, England: Elsevier Inc; 2013. 10.1016/B978-0-12-420067-8.00012-X.Search in Google Scholar PubMed

[65] Reddy KP, Kumar KB, Subhani SM, Khan PA. Effect of light and benzyladenine on dark‐treated growing rice leaves (Oryza sativa). I. Changes in chlorophyll content and catalase activity. Physiol Plant. 1985;63:79–86. 10.1111/j.1399-3054.1985.tb02822.x.Search in Google Scholar

[66] Soysal Ç, Söylemez Z. Kinetics and inactivation of carrot peroxidase by heat treatment. J Food Eng. 2005;68:349–56. 10.1016/j.jfoodeng.2004.06.009.Search in Google Scholar

[67] Converso DA, Fernández ME. Peroxidase isozymes from wheat germ: purification and properties. Phytochemistry. 1995;40:1341–5. 10.1016/0031-9422(95)00366-F.Search in Google Scholar

[68] Hashem A, Abd-Allah EF, Alqarawi AA, Egamberdieva D. Bioremediation of adverse impact of cadmium toxicity on Cassia italica Mill by arbuscular mycorrhizal fungi. Saudi J Biol Sci. 2016;23:39–47. 10.1016/j.sjbs.2015.11.007.Search in Google Scholar PubMed PubMed Central

[69] Bose BC, Vijayvargiya R. Spectrophotometric method for the estimation of guanethidine. J Pharm Pharmacol. 1964;16:561–2. 10.1111/j.2042-7158.1964.tb07513.x.Search in Google Scholar PubMed

[70] Hadwan MH. Simple spectrophotometric assay for measuring catalase activity in biological tissues. BMC Biochem. 2018;19:1–8. 10.1186/s12858-018-0097-5.Search in Google Scholar PubMed PubMed Central

[71] Boo HO, Heo BG, Gorinstein S, Chon SU. Positive effects of temperature and growth conditions on enzymatic and antioxidant status in lettuce plants. Plant Sci. 2011;181:479–84. 10.1016/j.plantsci.2011.07.013.Search in Google Scholar PubMed

[72] Kuvalekar A, Redkar A, Gandhe K, Harsulkar A. Peroxidase and polyphenol oxidase activities in compatible host-pathogen interaction in Jasminum officinale and Uromyces hobsoni: Insights into susceptibility of host. New Zeal J Bot. 2011;49:351–9. 10.1080/0028825X.2011.569727.Search in Google Scholar

[73] Malairuang K, Krajang M, Sukna J, Rattanapradit K, Chamsart S. High cell density cultivation of saccharomyces cerevisiae with intensive multiple sequential batches together with a novel technique of fed-batch at cell level (FBC). Processes. 2020;8:1–26. 10.3390/pr8101321.Search in Google Scholar

[74] Huang RY, Kowalski D, Minderman H, Gandhi N, Johnson ES. Small ubiquitin-related modifier pathway is a major determinant of doxorubicin cytotoxicity in Saccharomyces cerevisiae. Cancer Res. 2007;67:765–72. 10.1158/0008-5472.CAN-06-2839.Search in Google Scholar PubMed

[75] Buschini A, Poli P, Rossi C. Saccharomyces cerevisiae as an eukaryotic cell model to assess cytotoxicity and genotoxicity of three anticancer anthraquinones. Mutagenesis. 2003;18:25–36. 10.1093/mutage/18.1.25.Search in Google Scholar PubMed

[76] Li X, Shi X, Zou M, Luo Y, Tan Y, Wu Y, et al. Characteristics of morphological and physiological changes during the autolysis process of Saccharomyces cerevisiae FX-2. Korean J Microbiol Biotechnol. 2015;43:249–58. 10.4014/mbl.1503.03007.Search in Google Scholar

[77] Nasir A, Rahman SS, Hossain MM, Choudhury N. Isolation of Saccharomyces cerevisiae from pineapple and orange and study of metal’s effectiveness on ethanol production. Eur J Microbiol Immunol. 2017;7:76–91. 10.1556/1886.2016.00035.Search in Google Scholar PubMed PubMed Central

[78] Turan M, Nikerel E, Kaya K, Kitir N, Gunes A, Mokhtari NEP, et al. Enzyme dynamic in plant nutrition uptake and plant nutrition. Enzym Inhib Act. 2017;1–19. 10.5772/66938.Search in Google Scholar

[79] Sakkos JK, Wackett LP, Aksan A. Enhancement of biocatalyst activity and protection against stressors using a microbial exoskeleton. Sci Rep. 2019;9:1–12. 10.1038/s41598-019-40113-8.Search in Google Scholar PubMed PubMed Central

[80] Torres E, Ayala M. Biocatalysis based on heme peroxidases: Peroxidases as potential industrial biocatalysts. Berlin, Heidelberg: Springer Berlin Heidelberg; 2010. p. 1–358. 10.1007/978-3-642-12627-7.Search in Google Scholar

[81] Zhao F, Masci D, Ferla S, Varricchio C, Brancale A, Colonna S, et al. Monoamine oxidase (MAO-N) biocatalyzed synthesis of indoles from indolines prepared via photocatalytic cyclization/arylative dearomatization. ACS Catal. 2020;10:6414–21. 10.1021/acscatal.0c01351.Search in Google Scholar

[82] Jordan A, Hall CGJ, Thorp LR, Sneddon HF. Replacement of less-preferred dipolar aprotic and ethereal solvents in synthetic organic chemistry with more sustainable alternatives. Chem Rev. 2022;122:6749–94. 10.1021/acs.chemrev.1c00672.Search in Google Scholar PubMed PubMed Central

[83] Hui J, Ma Y, Zhao J, Cao H. Recent advances in the synthesis of indolizine and its derivatives by radical cyclization/cross-coupling. Org Biomol Chem. 2021;19:10245–58. 10.1039/d1ob01431e.Search in Google Scholar PubMed

[84] Feng J, Geng WC, Jiang H, Wu B. Recent advances in biocatalysis of nitrogen-containing heterocycles. Biotechnol Adv. 2022;54:107813. 10.1016/j.biotechadv.2021.107813.Search in Google Scholar PubMed

[85] Banik BK, Sahoo BM. Reactions in water: synthesis of biologically active compounds. London, England: Elsevier Inc; 2020. 10.1016/b978-0-12-817592-7.00013-7.Search in Google Scholar

[86] Druta II, Dinica RM, Bacu E, Humelnicu I. Synthesis of 7,7′-bisindolizines by the reaction of 4,4′-bipyridinium-ylides with activated alkynes. Tetrahedron. 1998;54:10811–8.10.1016/S0040-4020(98)00605-XSearch in Google Scholar

[87] Feng G, Wu H, Li X, Lai F, Zhao G, Yang M, et al. A new, efficient and highly-regioselective approach to synthesis of 6-O-propionyl-d-glucose by using whole-cell biocatalysts. Biochem Eng J. 2015;95:56–61. 10.1016/j.bej.2014.12.008.Search in Google Scholar

[88] Doble M, Kruthiventi AK. Biocatalysis: Green chemistry. Green Chem Eng. 2007;69–91. 10.1016/b978-012372532-5/50005-5.Search in Google Scholar

[89] Eduardo T, Marcela A. Biocatalysis Based on Heme Peroxidases. Vol. 53. Berlin, Heidelberg: Springer Berlin Heidelberg; 2010. 10.1007/978-3-642-12627-7.Search in Google Scholar

[90] Khanmohammadi M, Dastjerdi MB, Ai A, Ahmadi A, Godarzi A, Rahimi A, et al. Horseradish peroxidase-catalyzed hydrogelation for biomedical applications. Biomater Sci. 2018;6:1286–98. 10.1039/c8bm00056e.Search in Google Scholar PubMed

[91] Guo J, Liu Y, Zha J, Han H, Chen Y, Jia Z. Enhancing the peroxidase-mimicking activity of hemin by covalent immobilization in polymer nanogels. Polym Chem. 2021;12:858–66. 10.1039/d0py01465f.Search in Google Scholar

[92] Jörgensen S, Lindsjö J, Weber EM, Röcklinsberg H. Reviewing the review: A pilot study of the ethical review process of animal research in sweden. Animals. 2021;11:1–28. 10.3390/ani11030708.Search in Google Scholar PubMed PubMed Central

[93] Doke SK, Dhawale SC. Alternatives to animal testing: A review. Saudi Pharm J. 2015;23:223–9. 10.1016/j.jsps.2013.11.002.Search in Google Scholar PubMed PubMed Central

[94] Graham ML, Prescott MJ. The multifactorial role of the 3Rs in shifting the harm-benefit analysis in animal models of disease. Eur J Pharmacol. 2015;759:19–29. 10.1016/j.ejphar.2015.03.040.Search in Google Scholar PubMed PubMed Central

[95] Poletto NP, Rosado JO, Bonatto D. Evaluation of cytotoxic and cytostatic effects in Saccharomyces cerevisiae by poissoner quantitative drop test. Basic Clin Pharmacol Toxicol. 2009;104:71–5. 10.1111/j.1742-7843.2008.00336.x.Search in Google Scholar PubMed

[96] Sajid M, Stone SR, Kaur P. Recent advances in heterologous synthesis paving way for future green-modular bioindustries: A review with special reference to isoflavonoids. Front Bioeng Biotechnol. 2021;9:1–18. 10.3389/fbioe.2021.673270.Search in Google Scholar PubMed PubMed Central

Received: 2023-03-15
Accepted: 2023-07-03
Published Online: 2023-09-26

© 2023 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. Research Articles
  2. Value-added utilization of coal fly ash and recycled polyvinyl chloride in door or window sub-frame composites
  3. High removal efficiency of volatile phenol from coking wastewater using coal gasification slag via optimized adsorption and multi-grade batch process
  4. Evolution of surface morphology and properties of diamond films by hydrogen plasma etching
  5. Removal efficiency of dibenzofuran using CuZn-zeolitic imidazole frameworks as a catalyst and adsorbent
  6. Rapid and efficient microwave-assisted extraction of Caesalpinia sappan Linn. heartwood and subsequent synthesis of gold nanoparticles
  7. The catalytic characteristics of 2-methylnaphthalene acylation with AlCl3 immobilized on Hβ as Lewis acid catalyst
  8. Biodegradation of synthetic PVP biofilms using natural materials and nanoparticles
  9. Rutin-loaded selenium nanoparticles modulated the redox status, inflammatory, and apoptotic pathways associated with pentylenetetrazole-induced epilepsy in mice
  10. Optimization of apigenin nanoparticles prepared by planetary ball milling: In vitro and in vivo studies
  11. Synthesis and characterization of silver nanoparticles using Origanum onites leaves: Cytotoxic, apoptotic, and necrotic effects on Capan-1, L929, and Caco-2 cell lines
  12. Exergy analysis of a conceptual CO2 capture process with an amine-based DES
  13. Construction of fluorescence system of felodipine–tetracyanovinyl–2,2′-bipyridine complex
  14. Excellent photocatalytic degradation of rhodamine B over Bi2O3 supported on Zn-MOF nanocomposites under visible light
  15. Optimization-based control strategy for a large-scale polyhydroxyalkanoates production in a fed-batch bioreactor using a coupled PDE–ODE system
  16. Effectiveness of pH and amount of Artemia urumiana extract on physical, chemical, and biological attributes of UV-fabricated biogold nanoparticles
  17. Geranium leaf-mediated synthesis of silver nanoparticles and their transcriptomic effects on Candida albicans
  18. Synthesis, characterization, anticancer, anti-inflammatory activities, and docking studies of 3,5-disubstituted thiadiazine-2-thiones
  19. Synthesis and stability of phospholipid-encapsulated nano-selenium
  20. Putative anti-proliferative effect of Indian mustard (Brassica juncea) seed and its nano-formulation
  21. Enrichment of low-grade phosphorites by the selective leaching method
  22. Electrochemical analysis of the dissolution of gold in a copper–ethylenediamine–thiosulfate system
  23. Characterisation of carbonate lake sediments as a potential filler for polymer composites
  24. Evaluation of nano-selenium biofortification characteristics of alfalfa (Medicago sativa L.)
  25. Quality of oil extracted by cold press from Nigella sativa seeds incorporated with rosemary extracts and pretreated by microwaves
  26. Heteropolyacid-loaded MOF-derived mesoporous zirconia catalyst for chemical degradation of rhodamine B
  27. Recovery of critical metals from carbonatite-type mineral wastes: Geochemical modeling investigation of (bio)hydrometallurgical leaching of REEs
  28. Photocatalytic properties of ZnFe-mixed oxides synthesized via a simple route for water remediation
  29. Attenuation of di(2-ethylhexyl)phthalate-induced hepatic and renal toxicity by naringin nanoparticles in a rat model
  30. Novel in situ synthesis of quaternary core–shell metallic sulfide nanocomposites for degradation of organic dyes and hydrogen production
  31. Microfluidic steam-based synthesis of luminescent carbon quantum dots as sensing probes for nitrite detection
  32. Transformation of eggshell waste to egg white protein solution, calcium chloride dihydrate, and eggshell membrane powder
  33. Preparation of Zr-MOFs for the adsorption of doxycycline hydrochloride from wastewater
  34. Green nanoarchitectonics of the silver nanocrystal potential for treating malaria and their cytotoxic effects on the kidney Vero cell line
  35. Carbon emissions analysis of producing modified asphalt with natural asphalt
  36. An efficient and green synthesis of 2-phenylquinazolin-4(3H)-ones via t-BuONa-mediated oxidative condensation of 2-aminobenzamides and benzyl alcohols under solvent- and transition metal-free conditions
  37. Chitosan nanoparticles loaded with mesosulfuron methyl and mesosulfuron methyl + florasulam + MCPA isooctyl to manage weeds of wheat (Triticum aestivum L.)
  38. Synergism between lignite and high-sulfur petroleum coke in CO2 gasification
  39. Facile aqueous synthesis of ZnCuInS/ZnS–ZnS QDs with enhanced photoluminescence lifetime for selective detection of Cu(ii) ions
  40. Rapid synthesis of copper nanoparticles using Nepeta cataria leaves: An eco-friendly management of disease-causing vectors and bacterial pathogens
  41. Study on the photoelectrocatalytic activity of reduced TiO2 nanotube films for removal of methyl orange
  42. Development of a fuzzy logic model for the prediction of spark-ignition engine performance and emission for gasoline–ethanol blends
  43. Micro-impact-induced mechano-chemical synthesis of organic precursors from FeC/FeN and carbonates/nitrates in water and its extension to nucleobases
  44. Green synthesis of strontium-doped tin dioxide (SrSnO2) nanoparticles using the Mahonia bealei leaf extract and evaluation of their anticancer and antimicrobial activities
  45. A study on the larvicidal and adulticidal potential of Cladostepus spongiosus macroalgae and green-fabricated silver nanoparticles against mosquito vectors
  46. Catalysts based on nickel salt heteropolytungstates for selective oxidation of diphenyl sulfide
  47. Powerful antibacterial nanocomposites from Corallina officinalis-mediated nanometals and chitosan nanoparticles against fish-borne pathogens
  48. Removal behavior of Zn and alkalis from blast furnace dust in pre-reduction sinter process
  49. Environmentally friendly synthesis and computational studies of novel class of acridinedione integrated spirothiopyrrolizidines/indolizidines
  50. The mechanisms of inhibition and lubrication of clean fracturing flowback fluids in water-based drilling fluids
  51. Adsorption/desorption performance of cellulose membrane for Pb(ii)
  52. A one-pot, multicomponent tandem synthesis of fused polycyclic pyrrolo[3,2-c]quinolinone/pyrrolizino[2,3-c]quinolinone hybrid heterocycles via environmentally benign solid state melt reaction
  53. Green synthesis of silver nanoparticles using durian rind extract and optical characteristics of surface plasmon resonance-based optical sensor for the detection of hydrogen peroxide
  54. Electrochemical analysis of copper-EDTA-ammonia-gold thiosulfate dissolution system
  55. Characterization of bio-oil production by microwave pyrolysis from cashew nut shells and Cassia fistula pods
  56. Green synthesis methods and characterization of bacterial cellulose/silver nanoparticle composites
  57. Photocatalytic research performance of zinc oxide/graphite phase carbon nitride catalyst and its application in environment
  58. Effect of phytogenic iron nanoparticles on the bio-fortification of wheat varieties
  59. In vitro anti-cancer and antimicrobial effects of manganese oxide nanoparticles synthesized using the Glycyrrhiza uralensis leaf extract on breast cancer cell lines
  60. Preparation of Pd/Ce(F)-MCM-48 catalysts and their catalytic performance of n-heptane isomerization
  61. Green “one-pot” fluorescent bis-indolizine synthesis with whole-cell plant biocatalysis
  62. Silica-titania mesoporous silicas of MCM-41 type as effective catalysts and photocatalysts for selective oxidation of diphenyl sulfide by H2O2
  63. Biosynthesis of zinc oxide nanoparticles from molted feathers of Pavo cristatus and their antibiofilm and anticancer activities
  64. Clean preparation of rutile from Ti-containing mixed molten slag by CO2 oxidation
  65. Synthesis and characterization of Pluronic F-127-coated titanium dioxide nanoparticles synthesized from extracts of Atractylodes macrocephala leaf for antioxidant, antimicrobial, and anticancer properties
  66. Effect of pretreatment with alkali on the anaerobic digestion characteristics of kitchen waste and analysis of microbial diversity
  67. Ameliorated antimicrobial, antioxidant, and anticancer properties by Plectranthus vettiveroides root extract-mediated green synthesis of chitosan nanoparticles
  68. Microwave-accelerated pretreatment technique in green extraction of oil and bioactive compounds from camelina seeds: Effectiveness and characterization
  69. Studies on the extraction performance of phorate by aptamer-functionalized magnetic nanoparticles in plasma samples
  70. Investigation of structural properties and antibacterial activity of AgO nanoparticle extract from Solanum nigrum/Mentha leaf extracts by green synthesis method
  71. Green fabrication of chitosan from marine crustaceans and mushroom waste: Toward sustainable resource utilization
  72. Synthesis, characterization, and evaluation of nanoparticles of clodinofop propargyl and fenoxaprop-P-ethyl on weed control, growth, and yield of wheat (Triticum aestivum L.)
  73. The enhanced adsorption properties of phosphorus from aqueous solutions using lanthanum modified synthetic zeolites
  74. Separation of graphene oxides of different sizes by multi-layer dialysis and anti-friction and lubrication performance
  75. Visible-light-assisted base-catalyzed, one-pot synthesis of highly functionalized cinnolines
  76. The experimental study on the air oxidation of 5-hydroxymethylfurfural to 2,5-furandicarboxylic acid with Co–Mn–Br system
  77. Highly efficient removal of tetracycline and methyl violet 2B from aqueous solution using the bimetallic FeZn-ZIFs catalyst
  78. A thermo-tolerant cellulase enzyme produced by Bacillus amyloliquefaciens M7, an insight into synthesis, optimization, characterization, and bio-polishing activity
  79. Exploration of ketone derivatives of succinimide for their antidiabetic potential: In vitro and in vivo approaches
  80. Ultrasound-assisted green synthesis and in silico study of 6-(4-(butylamino)-6-(diethylamino)-1,3,5-triazin-2-yl)oxypyridazine derivatives
  81. A study of the anticancer potential of Pluronic F-127 encapsulated Fe2O3 nanoparticles derived from Berberis vulgaris extract
  82. Biogenic synthesis of silver nanoparticles using Consolida orientalis flowers: Identification, catalytic degradation, and biological effect
  83. Initial assessment of the presence of plastic waste in some coastal mangrove forests in Vietnam
  84. Adsorption synergy electrocatalytic degradation of phenol by active oxygen-containing species generated in Co-coal based cathode and graphite anode
  85. Antibacterial, antifungal, antioxidant, and cytotoxicity activities of the aqueous extract of Syzygium aromaticum-mediated synthesized novel silver nanoparticles
  86. Synthesis of a silica matrix with ZnO nanoparticles for the fabrication of a recyclable photodegradation system to eliminate methylene blue dye
  87. Natural polymer fillers instead of dye and pigments: Pumice and scoria in PDMS fluid and elastomer composites
  88. Study on the preparation of glycerylphosphorylcholine by transesterification under supported sodium methoxide
  89. Wireless network handheld terminal-based green ecological sustainable design evaluation system: Improved data communication and reduced packet loss rate
  90. The optimization of hydrogel strength from cassava starch using oxidized sucrose as a crosslinking agent
  91. Green synthesis of silver nanoparticles using Saccharum officinarum leaf extract for antiviral paint
  92. Study on the reliability of nano-silver-coated tin solder joints for flip chips
  93. Environmentally sustainable analytical quality by design aided RP-HPLC method for the estimation of brilliant blue in commercial food samples employing a green-ultrasound-assisted extraction technique
  94. Anticancer and antimicrobial potential of zinc/sodium alginate/polyethylene glycol/d-pinitol nanocomposites against osteosarcoma MG-63 cells
  95. Nanoporous carbon@CoFe2O4 nanocomposite as a green absorbent for the adsorptive removal of Hg(ii) from aqueous solutions
  96. Characterization of silver sulfide nanoparticles from actinobacterial strain (M10A62) and its toxicity against lepidopteran and dipterans insect species
  97. Phyto-fabrication and characterization of silver nanoparticles using Withania somnifera: Investigating antioxidant potential
  98. Effect of e-waste nanofillers on the mechanical, thermal, and wear properties of epoxy-blend sisal woven fiber-reinforced composites
  99. Magnesium nanohydroxide (2D brucite) as a host matrix for thymol and carvacrol: Synthesis, characterization, and inhibition of foodborne pathogens
  100. Synergistic inhibitive effect of a hybrid zinc oxide-benzalkonium chloride composite on the corrosion of carbon steel in a sulfuric acidic solution
  101. Review Articles
  102. Role and the importance of green approach in biosynthesis of nanopropolis and effectiveness of propolis in the treatment of COVID-19 pandemic
  103. Gum tragacanth-mediated synthesis of metal nanoparticles, characterization, and their applications as a bactericide, catalyst, antioxidant, and peroxidase mimic
  104. Green-processed nano-biocomposite (ZnO–TiO2): Potential candidates for biomedical applications
  105. Reaction mechanisms in microwave-assisted lignin depolymerisation in hydrogen-donating solvents
  106. Recent progress on non-noble metal catalysts for the deoxydehydration of biomass-derived oxygenates
  107. Rapid Communication
  108. Phosphorus removal by iron–carbon microelectrolysis: A new way to achieve phosphorus recovery
  109. Special Issue: Biomolecules-derived synthesis of nanomaterials for environmental and biological applications (Guest Editors: Arpita Roy and Fernanda Maria Policarpo Tonelli)
  110. Biomolecules-derived synthesis of nanomaterials for environmental and biological applications
  111. Nano-encapsulated tanshinone IIA in PLGA-PEG-COOH inhibits apoptosis and inflammation in cerebral ischemia/reperfusion injury
  112. Green fabrication of silver nanoparticles using Melia azedarach ripened fruit extract, their characterization, and biological properties
  113. Green-synthesized nanoparticles and their therapeutic applications: A review
  114. Antioxidant, antibacterial, and cytotoxicity potential of synthesized silver nanoparticles from the Cassia alata leaf aqueous extract
  115. Green synthesis of silver nanoparticles using Callisia fragrans leaf extract and its anticancer activity against MCF-7, HepG2, KB, LU-1, and MKN-7 cell lines
  116. Algae-based green AgNPs, AuNPs, and FeNPs as potential nanoremediators
  117. Green synthesis of Kickxia elatine-induced silver nanoparticles and their role as anti-acetylcholinesterase in the treatment of Alzheimer’s disease
  118. Phytocrystallization of silver nanoparticles using Cassia alata flower extract for effective control of fungal skin pathogens
  119. Antibacterial wound dressing with hydrogel from chitosan and polyvinyl alcohol from the red cabbage extract loaded with silver nanoparticles
  120. Leveraging of mycogenic copper oxide nanostructures for disease management of Alternaria blight of Brassica juncea
  121. Nanoscale molecular reactions in microbiological medicines in modern medical applications
  122. Synthesis and characterization of ZnO/β-cyclodextrin/nicotinic acid nanocomposite and its biological and environmental application
  123. Green synthesis of silver nanoparticles via Taxus wallichiana Zucc. plant-derived Taxol: Novel utilization as anticancer, antioxidation, anti-inflammation, and antiurolithic potential
  124. Recyclability and catalytic characteristics of copper oxide nanoparticles derived from bougainvillea plant flower extract for biomedical application
  125. Phytofabrication, characterization, and evaluation of novel bioinspired selenium–iron (Se–Fe) nanocomposites using Allium sativum extract for bio-potential applications
  126. Erratum
  127. Erratum to “Synthesis, characterization, and evaluation of nanoparticles of clodinofop propargyl and fenoxaprop-P-ethyl on weed control, growth, and yield of wheat (Triticum aestivum L.)”
https://doi.org/10.1515/gps-2023-0046
Keywords for this article
biocatalysis; green synthesis; enzyme; indolizine; cytotoxicity screening
Creative Commons
BY 4.0

Articles in the same Issue

  1. Research Articles
  2. Value-added utilization of coal fly ash and recycled polyvinyl chloride in door or window sub-frame composites
  3. High removal efficiency of volatile phenol from coking wastewater using coal gasification slag via optimized adsorption and multi-grade batch process
  4. Evolution of surface morphology and properties of diamond films by hydrogen plasma etching
  5. Removal efficiency of dibenzofuran using CuZn-zeolitic imidazole frameworks as a catalyst and adsorbent
  6. Rapid and efficient microwave-assisted extraction of Caesalpinia sappan Linn. heartwood and subsequent synthesis of gold nanoparticles
  7. The catalytic characteristics of 2-methylnaphthalene acylation with AlCl3 immobilized on Hβ as Lewis acid catalyst
  8. Biodegradation of synthetic PVP biofilms using natural materials and nanoparticles
  9. Rutin-loaded selenium nanoparticles modulated the redox status, inflammatory, and apoptotic pathways associated with pentylenetetrazole-induced epilepsy in mice
  10. Optimization of apigenin nanoparticles prepared by planetary ball milling: In vitro and in vivo studies
  11. Synthesis and characterization of silver nanoparticles using Origanum onites leaves: Cytotoxic, apoptotic, and necrotic effects on Capan-1, L929, and Caco-2 cell lines
  12. Exergy analysis of a conceptual CO2 capture process with an amine-based DES
  13. Construction of fluorescence system of felodipine–tetracyanovinyl–2,2′-bipyridine complex
  14. Excellent photocatalytic degradation of rhodamine B over Bi2O3 supported on Zn-MOF nanocomposites under visible light
  15. Optimization-based control strategy for a large-scale polyhydroxyalkanoates production in a fed-batch bioreactor using a coupled PDE–ODE system
  16. Effectiveness of pH and amount of Artemia urumiana extract on physical, chemical, and biological attributes of UV-fabricated biogold nanoparticles
  17. Geranium leaf-mediated synthesis of silver nanoparticles and their transcriptomic effects on Candida albicans
  18. Synthesis, characterization, anticancer, anti-inflammatory activities, and docking studies of 3,5-disubstituted thiadiazine-2-thiones
  19. Synthesis and stability of phospholipid-encapsulated nano-selenium
  20. Putative anti-proliferative effect of Indian mustard (Brassica juncea) seed and its nano-formulation
  21. Enrichment of low-grade phosphorites by the selective leaching method
  22. Electrochemical analysis of the dissolution of gold in a copper–ethylenediamine–thiosulfate system
  23. Characterisation of carbonate lake sediments as a potential filler for polymer composites
  24. Evaluation of nano-selenium biofortification characteristics of alfalfa (Medicago sativa L.)
  25. Quality of oil extracted by cold press from Nigella sativa seeds incorporated with rosemary extracts and pretreated by microwaves
  26. Heteropolyacid-loaded MOF-derived mesoporous zirconia catalyst for chemical degradation of rhodamine B
  27. Recovery of critical metals from carbonatite-type mineral wastes: Geochemical modeling investigation of (bio)hydrometallurgical leaching of REEs
  28. Photocatalytic properties of ZnFe-mixed oxides synthesized via a simple route for water remediation
  29. Attenuation of di(2-ethylhexyl)phthalate-induced hepatic and renal toxicity by naringin nanoparticles in a rat model
  30. Novel in situ synthesis of quaternary core–shell metallic sulfide nanocomposites for degradation of organic dyes and hydrogen production
  31. Microfluidic steam-based synthesis of luminescent carbon quantum dots as sensing probes for nitrite detection
  32. Transformation of eggshell waste to egg white protein solution, calcium chloride dihydrate, and eggshell membrane powder
  33. Preparation of Zr-MOFs for the adsorption of doxycycline hydrochloride from wastewater
  34. Green nanoarchitectonics of the silver nanocrystal potential for treating malaria and their cytotoxic effects on the kidney Vero cell line
  35. Carbon emissions analysis of producing modified asphalt with natural asphalt
  36. An efficient and green synthesis of 2-phenylquinazolin-4(3H)-ones via t-BuONa-mediated oxidative condensation of 2-aminobenzamides and benzyl alcohols under solvent- and transition metal-free conditions
  37. Chitosan nanoparticles loaded with mesosulfuron methyl and mesosulfuron methyl + florasulam + MCPA isooctyl to manage weeds of wheat (Triticum aestivum L.)
  38. Synergism between lignite and high-sulfur petroleum coke in CO2 gasification
  39. Facile aqueous synthesis of ZnCuInS/ZnS–ZnS QDs with enhanced photoluminescence lifetime for selective detection of Cu(ii) ions
  40. Rapid synthesis of copper nanoparticles using Nepeta cataria leaves: An eco-friendly management of disease-causing vectors and bacterial pathogens
  41. Study on the photoelectrocatalytic activity of reduced TiO2 nanotube films for removal of methyl orange
  42. Development of a fuzzy logic model for the prediction of spark-ignition engine performance and emission for gasoline–ethanol blends
  43. Micro-impact-induced mechano-chemical synthesis of organic precursors from FeC/FeN and carbonates/nitrates in water and its extension to nucleobases
  44. Green synthesis of strontium-doped tin dioxide (SrSnO2) nanoparticles using the Mahonia bealei leaf extract and evaluation of their anticancer and antimicrobial activities
  45. A study on the larvicidal and adulticidal potential of Cladostepus spongiosus macroalgae and green-fabricated silver nanoparticles against mosquito vectors
  46. Catalysts based on nickel salt heteropolytungstates for selective oxidation of diphenyl sulfide
  47. Powerful antibacterial nanocomposites from Corallina officinalis-mediated nanometals and chitosan nanoparticles against fish-borne pathogens
  48. Removal behavior of Zn and alkalis from blast furnace dust in pre-reduction sinter process
  49. Environmentally friendly synthesis and computational studies of novel class of acridinedione integrated spirothiopyrrolizidines/indolizidines
  50. The mechanisms of inhibition and lubrication of clean fracturing flowback fluids in water-based drilling fluids
  51. Adsorption/desorption performance of cellulose membrane for Pb(ii)
  52. A one-pot, multicomponent tandem synthesis of fused polycyclic pyrrolo[3,2-c]quinolinone/pyrrolizino[2,3-c]quinolinone hybrid heterocycles via environmentally benign solid state melt reaction
  53. Green synthesis of silver nanoparticles using durian rind extract and optical characteristics of surface plasmon resonance-based optical sensor for the detection of hydrogen peroxide
  54. Electrochemical analysis of copper-EDTA-ammonia-gold thiosulfate dissolution system
  55. Characterization of bio-oil production by microwave pyrolysis from cashew nut shells and Cassia fistula pods
  56. Green synthesis methods and characterization of bacterial cellulose/silver nanoparticle composites
  57. Photocatalytic research performance of zinc oxide/graphite phase carbon nitride catalyst and its application in environment
  58. Effect of phytogenic iron nanoparticles on the bio-fortification of wheat varieties
  59. In vitro anti-cancer and antimicrobial effects of manganese oxide nanoparticles synthesized using the Glycyrrhiza uralensis leaf extract on breast cancer cell lines
  60. Preparation of Pd/Ce(F)-MCM-48 catalysts and their catalytic performance of n-heptane isomerization
  61. Green “one-pot” fluorescent bis-indolizine synthesis with whole-cell plant biocatalysis
  62. Silica-titania mesoporous silicas of MCM-41 type as effective catalysts and photocatalysts for selective oxidation of diphenyl sulfide by H2O2
  63. Biosynthesis of zinc oxide nanoparticles from molted feathers of Pavo cristatus and their antibiofilm and anticancer activities
  64. Clean preparation of rutile from Ti-containing mixed molten slag by CO2 oxidation
  65. Synthesis and characterization of Pluronic F-127-coated titanium dioxide nanoparticles synthesized from extracts of Atractylodes macrocephala leaf for antioxidant, antimicrobial, and anticancer properties
  66. Effect of pretreatment with alkali on the anaerobic digestion characteristics of kitchen waste and analysis of microbial diversity
  67. Ameliorated antimicrobial, antioxidant, and anticancer properties by Plectranthus vettiveroides root extract-mediated green synthesis of chitosan nanoparticles
  68. Microwave-accelerated pretreatment technique in green extraction of oil and bioactive compounds from camelina seeds: Effectiveness and characterization
  69. Studies on the extraction performance of phorate by aptamer-functionalized magnetic nanoparticles in plasma samples
  70. Investigation of structural properties and antibacterial activity of AgO nanoparticle extract from Solanum nigrum/Mentha leaf extracts by green synthesis method
  71. Green fabrication of chitosan from marine crustaceans and mushroom waste: Toward sustainable resource utilization
  72. Synthesis, characterization, and evaluation of nanoparticles of clodinofop propargyl and fenoxaprop-P-ethyl on weed control, growth, and yield of wheat (Triticum aestivum L.)
  73. The enhanced adsorption properties of phosphorus from aqueous solutions using lanthanum modified synthetic zeolites
  74. Separation of graphene oxides of different sizes by multi-layer dialysis and anti-friction and lubrication performance
  75. Visible-light-assisted base-catalyzed, one-pot synthesis of highly functionalized cinnolines
  76. The experimental study on the air oxidation of 5-hydroxymethylfurfural to 2,5-furandicarboxylic acid with Co–Mn–Br system
  77. Highly efficient removal of tetracycline and methyl violet 2B from aqueous solution using the bimetallic FeZn-ZIFs catalyst
  78. A thermo-tolerant cellulase enzyme produced by Bacillus amyloliquefaciens M7, an insight into synthesis, optimization, characterization, and bio-polishing activity
  79. Exploration of ketone derivatives of succinimide for their antidiabetic potential: In vitro and in vivo approaches
  80. Ultrasound-assisted green synthesis and in silico study of 6-(4-(butylamino)-6-(diethylamino)-1,3,5-triazin-2-yl)oxypyridazine derivatives
  81. A study of the anticancer potential of Pluronic F-127 encapsulated Fe2O3 nanoparticles derived from Berberis vulgaris extract
  82. Biogenic synthesis of silver nanoparticles using Consolida orientalis flowers: Identification, catalytic degradation, and biological effect
  83. Initial assessment of the presence of plastic waste in some coastal mangrove forests in Vietnam
  84. Adsorption synergy electrocatalytic degradation of phenol by active oxygen-containing species generated in Co-coal based cathode and graphite anode
  85. Antibacterial, antifungal, antioxidant, and cytotoxicity activities of the aqueous extract of Syzygium aromaticum-mediated synthesized novel silver nanoparticles
  86. Synthesis of a silica matrix with ZnO nanoparticles for the fabrication of a recyclable photodegradation system to eliminate methylene blue dye
  87. Natural polymer fillers instead of dye and pigments: Pumice and scoria in PDMS fluid and elastomer composites
  88. Study on the preparation of glycerylphosphorylcholine by transesterification under supported sodium methoxide
  89. Wireless network handheld terminal-based green ecological sustainable design evaluation system: Improved data communication and reduced packet loss rate
  90. The optimization of hydrogel strength from cassava starch using oxidized sucrose as a crosslinking agent
  91. Green synthesis of silver nanoparticles using Saccharum officinarum leaf extract for antiviral paint
  92. Study on the reliability of nano-silver-coated tin solder joints for flip chips
  93. Environmentally sustainable analytical quality by design aided RP-HPLC method for the estimation of brilliant blue in commercial food samples employing a green-ultrasound-assisted extraction technique
  94. Anticancer and antimicrobial potential of zinc/sodium alginate/polyethylene glycol/d-pinitol nanocomposites against osteosarcoma MG-63 cells
  95. Nanoporous carbon@CoFe2O4 nanocomposite as a green absorbent for the adsorptive removal of Hg(ii) from aqueous solutions
  96. Characterization of silver sulfide nanoparticles from actinobacterial strain (M10A62) and its toxicity against lepidopteran and dipterans insect species
  97. Phyto-fabrication and characterization of silver nanoparticles using Withania somnifera: Investigating antioxidant potential
  98. Effect of e-waste nanofillers on the mechanical, thermal, and wear properties of epoxy-blend sisal woven fiber-reinforced composites
  99. Magnesium nanohydroxide (2D brucite) as a host matrix for thymol and carvacrol: Synthesis, characterization, and inhibition of foodborne pathogens
  100. Synergistic inhibitive effect of a hybrid zinc oxide-benzalkonium chloride composite on the corrosion of carbon steel in a sulfuric acidic solution
  101. Review Articles
  102. Role and the importance of green approach in biosynthesis of nanopropolis and effectiveness of propolis in the treatment of COVID-19 pandemic
  103. Gum tragacanth-mediated synthesis of metal nanoparticles, characterization, and their applications as a bactericide, catalyst, antioxidant, and peroxidase mimic
  104. Green-processed nano-biocomposite (ZnO–TiO2): Potential candidates for biomedical applications
  105. Reaction mechanisms in microwave-assisted lignin depolymerisation in hydrogen-donating solvents
  106. Recent progress on non-noble metal catalysts for the deoxydehydration of biomass-derived oxygenates
  107. Rapid Communication
  108. Phosphorus removal by iron–carbon microelectrolysis: A new way to achieve phosphorus recovery
  109. Special Issue: Biomolecules-derived synthesis of nanomaterials for environmental and biological applications (Guest Editors: Arpita Roy and Fernanda Maria Policarpo Tonelli)
  110. Biomolecules-derived synthesis of nanomaterials for environmental and biological applications
  111. Nano-encapsulated tanshinone IIA in PLGA-PEG-COOH inhibits apoptosis and inflammation in cerebral ischemia/reperfusion injury
  112. Green fabrication of silver nanoparticles using Melia azedarach ripened fruit extract, their characterization, and biological properties
  113. Green-synthesized nanoparticles and their therapeutic applications: A review
  114. Antioxidant, antibacterial, and cytotoxicity potential of synthesized silver nanoparticles from the Cassia alata leaf aqueous extract
  115. Green synthesis of silver nanoparticles using Callisia fragrans leaf extract and its anticancer activity against MCF-7, HepG2, KB, LU-1, and MKN-7 cell lines
  116. Algae-based green AgNPs, AuNPs, and FeNPs as potential nanoremediators
  117. Green synthesis of Kickxia elatine-induced silver nanoparticles and their role as anti-acetylcholinesterase in the treatment of Alzheimer’s disease
  118. Phytocrystallization of silver nanoparticles using Cassia alata flower extract for effective control of fungal skin pathogens
  119. Antibacterial wound dressing with hydrogel from chitosan and polyvinyl alcohol from the red cabbage extract loaded with silver nanoparticles
  120. Leveraging of mycogenic copper oxide nanostructures for disease management of Alternaria blight of Brassica juncea
  121. Nanoscale molecular reactions in microbiological medicines in modern medical applications
  122. Synthesis and characterization of ZnO/β-cyclodextrin/nicotinic acid nanocomposite and its biological and environmental application
  123. Green synthesis of silver nanoparticles via Taxus wallichiana Zucc. plant-derived Taxol: Novel utilization as anticancer, antioxidation, anti-inflammation, and antiurolithic potential
  124. Recyclability and catalytic characteristics of copper oxide nanoparticles derived from bougainvillea plant flower extract for biomedical application
  125. Phytofabrication, characterization, and evaluation of novel bioinspired selenium–iron (Se–Fe) nanocomposites using Allium sativum extract for bio-potential applications
  126. Erratum
  127. Erratum to “Synthesis, characterization, and evaluation of nanoparticles of clodinofop propargyl and fenoxaprop-P-ethyl on weed control, growth, and yield of wheat (Triticum aestivum L.)”
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 3.12.2025 from https://www.degruyterbrill.com/document/doi/10.1515/gps-2023-0046/html?lang=en
Scroll to top button