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Abstract In this work, we have reported the design, synthesis, in vitro, and in silico enzymatic evaluation of new bis-4-hydroxycoumarin-based phenoxy-1,2,3-triazole-N-phenylacetamide derivatives 5a-m as potent α-glucosidase inhibitors. All the synthesized analogues showed high inhibition effects against α-glucosidase (IC50 values ranging between 6.0 ± 0.2 and 85.4 ± 2.3 µM) as compared to the positive control acarbose (IC50 = 750.0 ± 0.6 µM). Among the newly synthesized compounds 5a-m, 2,4-dichloro-N-phenylacetamide derivative 5i with inhibition effect around 125-folds more than the acarbose was identified as the most potent entry. A structure–activity relationship (SAR) study about the title compounds 5a-m demonstrated that the inhibition effects of these compounds depend on the pattern of substitution on the N-phenylacetamide ring. The interaction modes and binding energies in the active site of enzyme of the important analogues (in term of SAR study) were evaluated through molecular docking study. Molecular dynamics and prediction of pharmacokinetic properties and toxicity of the most potent compound 5i also evaluated and the obtained data was compared with the acarbose.

Abstract In this work, a novel series of N-phenylacetamide-1,2,3-triazole-indole-2-carboxamide derivatives 5a–n were designed by consideration of the potent α-glucosidase inhibitors containing indole and carboxamide-1,2,3-triazole-N-phenylacetamide moieties. These compounds were synthesized by click reaction and evaluated against yeast α-glucosidase. All the newly title compounds demonstrated superior potency when compared with acarbose as a standard inhibitor. Particularly, compound 5k possessed the best inhibitory activity against α-glucosidase with around a 28-fold improvement in the inhibition effect in comparison standard inhibitor. This compound showed a competitive type of inhibition in the kinetics. The molecular docking and dynamics demonstrated that compound 5k with a favorable binding energy well occupied the active site of α-glucosidase.

Type 2 diabetes is a common condition that causes the level of glucose in the blood to become too high and α-glucosidase inhibitors are therapeutic agents in managing type 2 diabetes. In the present study, we report a new series of 3-aceto(benzo)hydrazide-1,2,4-triazine analogs as potential therapeutic agents against type 2 diabetes. In the in vitro evaluations, most compounds showed much stronger α-glucosidase inhibitory activity than the standard drug acarbose. Especially, compound 2A, (N'-(5,6-diphenyl-1,2,4-triazin-3-yl)-4-methoxybenzohydrazide) as the most active compound showed IC50 = 12.0 μM which is 60 folds more potent than acarbose. In addition, the MTT test using the three cell lines HCT-116, MDA-MB-231, and A549 showed that the target compounds have low cytotoxic effects with IC50 values in the range of 60–280 μM, therefore they can be considered as safe compounds. Molecular docking studies predicted that the strong inhibitory activity of 2A is related to the interactions generated by the three residues Asp282, Trp481, and Asp616 with the triazine core and hydrazide motif in the active site of the enzyme. The significant inhibitory effect of 2A against α-glucosidase was also confirmed in vivo, where the compound showed equivalent activity to the standard drug acarbose on reducing blood glucose in the tested mice. In conclusion, this study introduces compound 2A as a new lead compound with favorable cytotoxicity, strong α-glucosidase inhibitory activity and in vivo hypoglycemic effect, for future investigation in the treatment of diabetes mellitus.

One of the multifactorial worldwide health syndromes is diabetes mellitus which is increasing at a disturbing rate. The inhibition of α-glucosidase, an enzyme that catalyzes starch hydrolysis in the intestine, is one helpful therapeutic approach for controlling hyperglycemia related to type-2 diabetes. To discover α-glucosidase inhibitors, some 2-hydrazolyl-4-thiazolidinone hybrids (3a-e) were synthesized from new one-pot reaction procedures. Next, their chemical structures were confirmed by 1H NMR, 13C NMR, and FT-IR spectra, and elemental analysis technique. Then, the α-glucosidase inhibitory activity of the titled compounds was evaluated. Among them, derivatives 3b and 3c revealed the highest activity against α-glucosidase compared to acarbose as a drug. Enzyme kinetic studies of the most active derivative (3b) indicated a competitive inhibition. Finally, molecular modeling studies were accomplished to describe vital interactions of the most potent compounds (3b and 3c) with the α-glucosidase enzyme.

Abstract Regarding the important role of α-glucosidase enzyme in the management of type 2 diabetes mellitus, the current study was established to design and synthesize aryl-quinoline-4-carbonyl hydrazone bearing different 2-methoxyphenoxyacetamide (11a–o) and the structure of all derivatives was confirmed through various techniques including IR, 1H-NMR, 13C-NMR and elemental analysis. Next, the α-glucosidase inhibitory potentials of all derivatives were evaluated, and all compounds displayed potent inhibition with IC50 values in the range of 26.0 ± 0.8–459.8 ± 1.5 µM as compared to acarbose used as control, except 11f and 11l. Additionally, in silico-induced fit docking and molecular dynamics studies were performed to further investigate the interaction, orientation, and conformation of the newly synthesized compounds over the active site of α-glucosidase.

Abstract Diabetes mellitus is a multifactorial global health disorder that is rising at an alarming rate. One effective therapeutic approach for controlling hyperglycemia associated with type-2 diabetes is to target α-glucosidase, which catalyzes starch hydrolysis in the intestine. In an attempt to find potential α-glucosidase inhibitors, a series of twenty new quinoline linked benzothiazole hybrids (8a–t) were synthesized in good yields from suitable reaction procedures and their chemical structures were analyzed by 1HNMR, 13CNMR, IR, and ESI–MS analysis. The synthesized derivatives further screened for their activity against α-glucosidase. Among them, compounds 8b, 8h, 8n and 8o exhibited remarkable α-glucosidase inhibitory activity with IC50 values ranging from 38.2 ± 0.3 to 79.9 ± 1.2 µM compared with standard drug acarbose (IC50 = 750.0 ± 2.0 µM). Enzyme kinetic studies of the most active compound (8h) indicated a non-competitive inhibition with Ki value of 38.2 µM. Moreover, the homology modeling, molecular docking and molecular dynamics simulation studies were conducted to reveal key interactions between the most active compound 8h and the targeted enzyme. These results are complementary to the experimental observations. In order to predict the druggability of the novel derivatives, the pharmacokinetic properties were also applied. These findings could be useful for the design and development of new α-glucosidase inhibitors.

Abstract Analysis of food additives is highly significant in the food industry and directly related to human health. This investigation into the removal efficiency of sunset yellow as an azo dye in fruit juices using Chitosan-nickel ferrite nanoparticles (Cs@NiFe2O4 NPs). The nanoparticles were synthesized and characterized using various techniques. The effective parameters for removing sunset yellow were optimized using the response surface methodology (RSM) based on the central composite design (CCD). Under the optimum conditions, the highest removal efficiency (94.90%) was obtained for the initial dye concentration of 26.48 mg L−1 at a pH of 3.87, a reaction time of 67.62 min, and a nanoparticle dose of 0.038 g L−1. The pseudo-second-order kinetic model had a better fit for experimental data (R2 = 0.98) than the other kinetic models. The equilibrium adsorption process followed the Freundlich isotherm model with a maximum adsorption capacity of 212.766 mg g−1. The dye removal efficiency achieved for industrial and traditional fruit juice samples (91.75% and 93.24%), respectively, confirmed the method's performance, feasibility, and efficiency. The dye adsorption efficiency showed no significant decrease after five recycling, indicating that the sorbent has suitable stability in practical applications. variousThe synthesized nanoparticles can be suggested as an efficient sorbent to remove the sunset yellow dye from food products.

Abstract A novel nanomagnet modified with nickel ferrite nanoparticles (NPs) coated with hybrid chitosan (Cs–NiFe2O4) was synthesized using the co-precipitation method. The resulting nanomagnets were characterized using various techniques. The size of the nanomagnetic particles was estimated to be about 40 nm based on the transmission electron microscopy (TEM) image and X-ray diffraction analysis (XRD) pattern (using the Debye–Scherrer equation). Scanning electron microscopy (SEM) images indicated that the surface of Cs–NiFe2O4 NPs is flatter and smoother than the uncoated NiFe2O4 NPs. According to value stream mapping (VSM) analysis, the magnetization value of Cs–NiFe2O4 NPs (17.34 emu/g) was significantly lower than NiFe2O4 NPs (40.67 emu/g). The Cs–NiFe2O4 NPs indicated higher antibacterial properties than NiFe2O4 NPs and Cs. The minimum inhibitory concentrations of Cs–NiFe2O4 NPs against S. aureus and E. coli were 128 and 256 mg/mL, respectively. Antioxidant activity (evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging test) for NiFe2O4 NPs and Cs–NiFe2O4 NPs at the concentration of 100 µg/mL were 35% and 42%, respectively. Consequently, the synthesized Cs–NiFe2O4 NPs can be proposed as a viable material for biomedical applications.

Abstract α-Glucosidase inhibition is an approved treatment for type 2 diabetes mellitus (T2DM). In an attempt to develop novel anti-α-glucosidase agents, two series of substituted imidazo[1,2-c]quinazolines, namely 6a–c and 11a–o, were synthesized using a simple, straightforward synthetic routes. These compounds were thoroughly characterized by IR, 1H and 13C NMR spectroscopy, as well as mass spectrometry and elemental analysis. Subsequently, the inhibitory activities of these compounds were evaluated against Saccharomyces cerevisiae α-glucosidase. In present study, acarbose was utilized as a positive control. These imidazoquinazolines exhibited excellent to great inhibitory potencies with IC50 values ranging from 12.44 ± 0.38 μM to 308.33 ± 0.06 μM, which were several times more potent than standard drug with IC50 value of 750.0 ± 1.5 μM. Representatively, compound 11j showed remarkable anti-α-glucosidase potency with IC50 = 12.44 ± 0.38 μM, which was 60.3 times more potent than positive control acarbose. To explore the potential inhibition mechanism, further evaluations including kinetic analysis, circular dichroism, fluorescence spectroscopy, and thermodynamic profile were carried out for the most potent compound 11j. Moreover, molecular docking studies and in silico ADME prediction for all imidazoquinazolines 6a–c and 11a–o were performed to reveal their important binding interactions, as well as their physicochemical and drug-likeness properties, respectively.

Abstract α-Glucosidase as a carbohydrate-hydrolase enzyme is a crucial therapeutic target for type 2 diabetes. In this work, benzo[d]imidazole-amide containing 1,2,3-triazole-N-arylacetamide derivatives 8a–n were synthesized and evaluated for their inhibitory activity against α-glucosidase. In vitro α-glucosidase inhibition assay demonstrated that more than half of the title compounds with IC50 values in the range of 49.0–668.5 μM were more potent than standard inhibitor acarbose (IC50 = 750.0 µM). The most promising inhibitor was N-2-methylphenylacetamid derivative 8c. Kinetic study revealed that compound 8c (Ki = 40.0 µM) is a competitive inhibitor against α-glucosidase. Significantly, molecular docking and molecular dynamics studies on the most potent compound showed that this compound with a proper binding energy interacted with important amino acids of the α-glucosidase active site. Study on cytotoxicity of the most potent compounds 8c, 8e, and 8g demonstrated that these compounds did not show cytotoxic activity against the cancer and normal cell lines MCF-7 and HDF, respectively. Furthermore, the ADMET study predicted that compound 8c is likely to be orally active and non-cytotoxic.

Abstract An important target in the treatment of type 2 diabetes is α-glucosidase. Inhibition of this enzyme led to delay in glucose absorption and decrease in postprandial hyperglycemia. A new series of phthalimide-phenoxy-1,2,3-triazole-N-phenyl (or benzyl) acetamides 11a–n were designed based on the reported potent α-glucosidase inhibitors. These compounds were synthesized and screened for their in vitro inhibitory activity against the latter enzyme. The majority of the evaluated compounds displayed high inhibition effects (IC50 values in the range of 45.26 ± 0.03–491.68 ± 0.11 µM) as compared to the positive control acarbose (IC50 value = 750.1 ± 0.23 µM). Among this series, compounds 11j and 11i represented the most potent α-glucosidase inhibitory activities with IC50 values of 45.26 ± 0.03 and 46.25 ± 0.89 µM. Kinetic analysis revealed that the compound 11j is a competitive inhibitor with a Ki of 50.4 µM. Furthermore, the binding interactions of the most potent compounds in α-glucosidase active site were studied through molecular docking and molecular dynamics. The latter studies confirmed the obtained results through in vitro experiments. Furthermore, in silico pharmacokinetic study of the most potent compounds was also performed.

Organic-inorganic hybrid nanoflowers with flower-like morphology are new nanostructures comprising organic and inorganic components. In general, the organic component of hybrid nanoflowers mostly consists of proteins, DNA, RNA, plant extracts, metabolites, and natural polymers; and the inorganic component composes of various metal phosphates, including copper, calcium, manganese, iron, zinc, cobalt, cadmium, aluminum, silver, gold, etc. Until now, five notable procedures have been introduced for their synthesis, including biomineralization, ultra-fast sonication, the two-step method, shear stress, and the concentrated method. These nanostructures have many promising applications in diverse fields, such as the immobilization of enzymes and biomolecules, bio-catalysis of chemical reactions, bioremediation, electrochemical biosensors, drug and gene carriers, diagnosis of various diseases, photothermal therapy, etc., and wide range of research has been performed on them in the last recent decade. Google Scholar, Scopus, ScienceDirect, and Springer databases were searched using the keywords hybrid nanostructure, nanoflower, biosciences, and biocatalyst to find related articles. Studying these organic-inorganic hybrid nanocrystals may lead to finding new creative solutions in the effective application of enzyme-based systems, the rapid development of bionanomaterials, and biotechnology industries. The present review has investigated the different types of hybrid nanoflowers, their synthesis procedures and structural characteristics, and their applications in biosciences.

Abstract Background A new series of indole-carbohydrazide-phenoxy-1,2,3-triazole-N-phenylacetamide hybrids 11a–o was designed based on molecular hybridization of the active pharmacophores of the potent α-glucosidase inhibitors. These compounds were synthesized and evaluated against α-glucosidase. Methods The 15 various derivatives of indole-carbohydrazide-phenoxy-1,2,3-triazole-N-phenylacetamide scaffold were synthesized, purified, and fully characterized. These derivatives were evaluated against yeast α-glucosidase in vitro and in silico. ADMET properties of the most potent compounds were also predicted. Results All new derivatives 11a–o (IC50 values = 6.31 ± 0.03–49.89 ± 0.09 µM) are excellent α-glucosidase inhibitors in comparison to acarbose (IC50 value = 750.0 ± 10.0 µM) that was used as a positive control. Representatively, (E)-2-(4-((4-((2-(1H-indole-2-carbonyl)hydrazono)methyl) phenoxy)methyl)-1H-1,2,3-triazol-1-yl)-N-(4-methoxyphenyl)acetamide 11d with IC50 = 6.31 µM against MCF-7 cells, was 118.8-times more potent than acarbose. This compound is an uncompetitive inhibitor against α-glucosidase and showed the lowest binding energy at the active site of this enzyme in comparison to other potent compounds. Furthermore, computational calculations predicted that compound 11d can be an orally active compound. Conclusion According to obtained data, compound 11d can be a valuable lead compound for further structural development and assessments to obtain effective and potent new α-glucosidase inhibitors.

Abstract Background The plants from Salvia genus contain widely distributed species which have been used in folk medicine as well as pharmaceutical and food industries. Methods The chemical composition of 12 native Iranian Salvia species (14 plants) was identified using gas chromatography-mass spectrometry (GC–MS). Also, the inhibitory activity of all essential oils (EOs) was evaluated toward α-glucosidase and two types of cholinesterase (ChE) using spectrophotometric methods. The in vitro α-glucosidase inhibition assay was performed by the determination of p-nitrophenol (pNP) obtained from the enzymatic dissociation of p-nitrophenol-α-D-glucopyranoside (pNPG) as the substrate. In vitro ChE inhibitory assay was conducted based on the modified Ellman’s procedure using the measurement of 5-thio-2-nitrobenzoic acid produced from the hydrolysis of thiocholine derivatives as the substrate, in the presence of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Results Totally, 139 compounds were detected and caryophyllene oxide and trans-β-caryophyllene were the most abundant compounds in all EOs. The yield of EOs extracted from the plants were also calculated in the range of 0.06 to 0.96% w/w. Herein, α-glucosidase inhibitory activity of 8 EOs was reported for the first time and among all, S. spinosa L. was found to be the most potent inhibitor (90.5 inhibition at 500 μg/mL). Also, the ChE inhibitory activity of 8 species was reported for the first time and our results showed that the BChE inhibitory effect of all EOs was more potent than that of AChE. The ChE inhibition assay indicated that S. mirzayanii Rech.f. & Esfand. collected from Shiraz was the most potent inhibitor (72.68% and 40.6% at the concentration of 500 μg/mL, toward AChE and BChE, respectively). Conclusions It seems that native Salvia species of Iran could be considered in the development of anti-diabetic and anti-Alzheimer's disease supplements.

Abstract Herein, various N′-substituted benzylidene benzohydrazide-1,2,3-triazoles were designed, synthesized, and screened for their inhibitory activity toward α-glucosidase. The structure of derivatives was confirmed using 1H- and 13C-NMR, FTIR, Mass spectrometry, and elemental analysis. All derivatives exhibited good inhibition with IC50 values in the range of 0.01 to 648.90 µM, compared with acarbose as the positive control (IC50 = 752.10 µM). Among them, compounds 7a and 7h showed significant potency with IC50 values of 0.02 and 0.01 µM, respectively. The kinetic study revealed that they are noncompetitive inhibitors toward α-glucosidase. Also, fluorescence quenching was used to investigate the interaction of three inhibitors 7a, 7d, and 7h, with α-glucosidase. Accordingly, the binding constants, the number of binding sites, and values of thermodynamic parameters were determined for the interaction of candidate compounds toward the enzyme. Finally, the in silico cavity detection plus molecular docking was performed to find the allosteric site and key interactions between synthesized compounds and the target enzyme.

Abstract New series of thioquinoline structures bearing phenylacetamide 9a–p were designed, synthesized and the structure of all derivatives was confirmed using different spectroscopic techniques including FTIR, 1H-NMR, 13C-NMR, ESI–MS and elemental analysis. Next, the α-glucosidase inhibitory activities of derivatives were also determined and all the synthesized compounds (IC50 = 14.0 ± 0.6–373.85 ± 0.8 μM) were more potent than standard inhibitors acarbose (IC50 = 752.0 ± 2.0 μM) against α-glucosidase. Structure–activity relationships (SARs) were rationalized by analyzing the substituents effects and it was shown that mostly, electron-donating groups at the R position are more favorable compared to the electron-withdrawing group. Kinetic studies of the most potent derivative, 9m, carrying 2,6-dimethylphenyl exhibited a competitive mode of inhibition with K i value of 18.0 µM. Furthermore, based on the molecular dynamic studies, compound 9m depicted noticeable interactions with the α-glucosidase active site via several H-bound, hydrophobic and hydrophilic interactions. These interactions cause interfering catalytic potential which significantly decreased the α-glucosidase activity.

Abstract In the present study, new structural variants of 4-hydroxyquinolinone-hydrazones were designed and synthesized. The structure elucidation of the synthetic derivatives 6a–o was carried out using different spectroscopic techniques including FTIR, 1H-NMR, 13C-NMR, and elemental analysis, and their α-glucosidase inhibitory activity was also determined. The synthetic molecules 6a–o exhibited good α-glucosidase inhibition with IC50 values ranging between 93.5 ± 0.6 to 575.6 ± 0.4 µM as compared to the standard acarbose (IC50 = 752.0 ± 2.0 µM). Structure–activity relationships of this series were established which is mainly based on the position and nature of the substituent on the benzylidene ring. A kinetic study of the active compounds 6l and 6m as the most potent derivatives were also carried out to confirm the mode of inhibition. The binding interactions of the most active compounds within the active site of the enzyme were determined by molecular docking and molecular dynamic simulations.

Abstract In this article, different s-substituted benzimidazole-thioquinoline derivatives were designed, synthesized, and evaluated for their possible α-glucosidase inhibitory activities. The most active compound in this series, 6j (X = 4-bromobenzyl) exhibited significant potency with an IC50 value of 28.0 ± 0.6 µM compared to acarbose as the positive control with an IC50 value of 750.0 µM. The kinetic study showed a competitive inhibition pattern against α-glucosidase for the 6j derivative. Also, the molecular dynamic simulations were performed to determine key interactions between compounds and the targeted enzyme. The in silico pharmacodynamics and ADMET properties were executed to illustrate the druggability of the novel derivatives. In general, it can be concluded that these derivatives can serve as promising leads to the design of potential α-glucosidase inhibitors.

Abstract The development of new antidiabetes agents is necessary to obtain optimal glycemic control and overcome its complications. Different quinazolin-4(3H)-one bearing phenoxy-acetamide derivatives (7a–r) were designed and synthesized to develop α-glucosidase inhibitors. All the synthesized derivatives were evaluated against α-glucosidase in vitro and among them, compound 7b showed the highest α-glucosidase inhibition with an IC50 of 14.4 µM, which was ∼53 times stronger than that of acarbose. The inhibition kinetic studies showed that the inhibitory mechanism of compound 7b was a competitive type towards α-glucosidase. Also, molecular docking studies analyzed the interaction between the most potent derivative and α-glucosidase. Current findings indicate the new potential of quinazolin-4(3H)-ones that could be used for the development of novel agents against diabetes mellitus.

Abstract Background A series of coumarin-indole hybrids was synthesized as the new α-glucosidase inhibitors. The title hybrids were considered as α-glucosidase inhibitors because had two active pharmacophores against α-glucosidase: coumarin and indole. Methods The thirteen various derivatives 4a–m were synthesized, purified, and fully characterized. These compounds were evaluated against α-glucosidase in vitro and in silico. In silico pharmacokinetic studies of the most potent compounds were also performed. Results Most of the title compounds exhibited high anti-α-glucosidase activity in comparison to standard drug acarbose. In particular, the phenoxy derivative 4d namely 3-((1H-indol-3-yl)(3-phenoxyphenyl)methyl)-4-hydroxy-2H-chromen-2-one showed promising activity. This compound is a competitive inhibitor against α-glucosidase and showed the lowest binding energy at the α-glucosidase active site in comparison to other potent synthesized compounds and acarbose. Conclusion Compound 4d can be a lead compound for further structural development to obtain effective and potent α-glucosidase inhibitors.

Abstract The control of postprandial hyperglycemia is an important target in the treatment of type 2 diabetes mellitus (T2DM). As a result, targeting α-glucosidase as the most important enzyme in the breakdown of carbohydrates to glucose that leads to an increase in postprandial hyperglycemia is one of the treatment processes of T2DM. In the present work, a new class of benzimidazole-Schiff base hybrids 8a–p has been developed based on the potent reported α-glucosidase inhibitors. These compounds were synthesized by sample recantations, characterized by 1H-NMR, 13C-NMR, FT-IR, and CHNS elemental analysis, and evaluated against α-glucosidase. All new compounds, with the exception of inactive compound 8g, showed excellent inhibitory activities (60.1 ± 3.6–287.1 ± 7.4 µM) in comparison to acarbose as the positive control (750.0 ± 10.5). Kinetic study of the most potent compound 8p showed a competitive type of inhibition (Ki value = 60 µM). In silico induced fit docking and molecular dynamics studies were performed to further investigate the interaction, orientation, and conformation of the title new compounds over the active site of α-glucosidase. In silico druglikeness analysis and ADMET prediction of the most potent compounds demonstrated that these compounds were druglikeness and had satisfactory ADMET profile.

Abstract In this study, 18 novel quinoline-based-benzo[d]imidazole derivatives were synthesized and screened for their α-glucosidase inhibitory potential. All compounds in the series except 9q showed a significant α-glucosidase inhibition with IC50 values in the range of 3.2 ± 0.3–185.0 ± 0.3 µM, as compared to the standard drug acarbose (IC50 = 750.0 ± 5.0 µM). A kinetic study indicated that compound 9d as the most potent derivative against α-glucosidase was a competitive type inhibitor. Furthermore, the molecular docking study revealed the effective binding interactions of 9d with the active site of the α-glucosidase enzyme. The results indicate that the designed compounds have the potential to be further studied as new anti-diabetic agents.

Abstract A novel series of diphenylquinoxaline-6-carbohydrazide hybrids 7a–o were rationally designed and synthesized as anti-diabetic agents. All synthesized compounds 7a–o were screened as possible α-glucosidase inhibitors and exhibited good inhibitory activity with IC50 values in the range of 110.6 ± 6.0 to 453.0 ± 4.7 µM in comparison with acarbose as the positive control (750.0 ± 10.5 µM). An exception in this trend came back to a compound 7k with IC50 value > 750 µM. Furthermore, the most potent derivative 7e bearing 3-fluorophenyl moiety was further explored by kinetic studies and showed the competitive type of inhibition. Additionally, the molecular docking of all derivatives was performed to get an insight into the binding mode of these derivatives within the active site of the enzyme. In silico assessments exhibited that 7e was well occupied in the binding pocket of the enzyme through favorable interactions with residues, correlating to the experimental results.

Background and objectives: The oleoresin of Pistacia atlantica Desf. (known as “Baneh” in Iran) has been frequently used in traditional medicine for its medicinal properties. Herein, P. atlantica essential oil was investigated for its antimicrobial and α-glucosidase inhibitory activities since α-pinene which has been identified as the most abundant component in Pistacia genus oil, has demonstrated antimicrobial and anti-α-glucosidase properties. Methods: Fresh oleoresin was collected from Javanroud, Kermanshah, Iran and the essential oil was obtained by Clevenger-type apparatus. The chemical composition of essential oil was identified with GC/MS analysis and compared with those reported from various regions. The antimicrobial activity was evaluated against various strains (Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Candida albicans, Saccharomyces cerevisiae, and Lactobacilli spp.) through MIC method. Also, its anti-α-glucosidase property and antioxidant activity by DPPH assay were investigated. Results: GC/MS analysis of the essential oil confirmed the presence of nineteen compounds and among them, α-pinene (64.8%) was identified as the major constituent. Also, β-pinene (5.7%) and cis-limonene oxide (4.5%) were relatively abundant. Our results revealed antimicrobial properties of the “Baneh” essential oil against various bacterial and fungal strains. Moreover, it demonstrated inhibitory activity toward α-glucosidase with IC50 value of 41.5 ± 2.5 mg/mL compared with acarbose (IC50=0.5±0.2 mg/mL). DPPH free-radical scavenging activity assay showed antioxidant activity with IC50 value of 155.2 ± 1.4 mg/mL compared with quercetin (IC50=250.0±0.0 μg/mL). Conclusion: Pistacia atlantica oleoresin essential oil depicted satisfactory antimicrobial activity against both Gram-positive and Gram-negative strains. However, it demonstrated low antioxidant and α-glucosidase inhibitory effects.

Abstract In the present work, a new series of 14 novel phthalimide-benzenesulfonamide derivatives 4a–n were synthesized, and their inhibitory activity against yeast α-glucosidase was screened. The obtained results indicated that most of the newly synthesized compounds showed prominent inhibitory activity against α-glucosidase. Among them, 4-phenylpiperazin derivative 4m exhibited the strongest inhibition with the IC50 value of 52.2 ± 0.1 µM. Enzyme kinetic study of compound 4m proved that its inhibition mode was competitive and Ki value of this compound was calculated to be 52.7 µM. In silico induced fit docking and molecular dynamics studies were performed to further investigate the interaction, orientation, and conformation of the target compounds over the active site of α-glucosidase. Obtained date of these studies demonstrated that our new compounds interacted as well with the α-glucosidase active site with the acceptable binding energies. Furthermore, in silico druglikeness/ADME/Toxicity studies of compound 4m were performed and predicted that this compound is druglikeness and has good ADME and toxicity profiles.

Abstract A novel approach termed the "concentrated method" was developed for the instant fabrication of laccase@Co3(PO4)2•hybrid nanoflowers (HNFs). The constructed HNFs were obtained by optimizing the concentration of cobalt chloride and phosphate buffer to reach the highest activity recovery. The incorporation of 30 mM CoCl2 and 160 mM phosphate buffer (pH 7.4) resulted in a fast anisotropic growth of the nanomaterials. The purposed method did not involve harsh conditions and prolonged incubation of precursors, as the most reported approaches for the synthesis of HNFs. The catalytic efficiency of the immobilized and free laccase was 460 and 400 M−1S−1, respectively. Also, the enzymatic activity of the prepared biocatalyst was 113% of the free enzyme (0.5 U mL−1). The stability of the synthesized HNFs was enhanced by 400% at pH 6.5–9.5 and the elevated temperatures. The activity of laccase@Co3(PO4)2•HNFs declined to 50% of the initial value after 10 reusability cycles, indicating successful immobilization of the enzyme. Structural studies revealed a 32% increase in the α-helix content after hybridization with cobalt phosphate, which improved the activity and stability of the immobilized laccase. Furthermore, the fabricated HNFs exhibited a considerable ability to remove moxifloxacin as an emerging pollutant. The antibiotic (10 mg L−1) was removed by 24% and 75% after 24 h through adsorption and biodegradation, respectively. This study introduces a new method for synthesizing HNFs, which could be used for the fabrication of efficient biocatalysts, biosensors, and adsorbents for industrial, biomedical, and environmental applications.

Abstract In this work, a novel series of cyanoacetohydrazide linked to 1,2,3-triazoles (9a–n) were designed and synthesized to be evaluated for their anti-α-glucosidase activity, focusing on the fact that α-glucosidase inhibitors have played a significant role in the management of type 2 diabetes mellitus. All synthesized compounds except 9a exhibited excellent inhibitory potential, with IC50 values ranging from 1.00 ± 0.01 to 271.17 ± 0.30 μM when compared to the standard drug acarbose (IC50 = 754.1 ± 0.5 μM). The kinetic binding study indicated that the most active derivatives 9b (IC50 = 1.50 ± 0.01 μM) and 9e (IC50 = 1.00 ± 0.01 μM) behaved as the uncompetitive inhibitors of α-glucosidase with K i = 0.43 and 0.24 μM, respectively. Moreover, fluorescence measurements were conducted to show conformational changes of the enzyme after binding of the most potent inhibitor (9e). Calculation of standard enthalpy (ΔH m°) and entropy (ΔS m°) values confirmed the construction of hydrophobic interactions between 9e and the enzyme. Also, docking studies indicated desired interactions with important residues of the enzyme which rationalized the in vitro results.

Background and objectives: Medicinal plants have been considered as important sources of potent free radical scavengers as well as digestive enzymes inhibitors. Several plants are used in traditional and modern medicine for their biological properties such as anti-oxidant and anti-diabetic activity. The aim of this study was to investigate the anti-diabetic and anti-oxidant activities of roots and aerial parts from three of five native Iranian herbaceaous Geum species, including G. iranicum, G. kokanicum and G. urbanum. The Geum species and their bio-active substances are getting a lot of attention due to their various biological effects, such as anti-oxidant, anti-diabetic, anti-tumor and anti-microbial activities. Methods: The anti-diabetic activity of the Geum species was evaluated via α-glucosidase and α-amylase inhibition assays. The anti-oxidant effect was analyzed using the free radical scavenging method and the total phenolics content was determined via a colorimetric assay. Results: Based on our study, all the examined species revealed moderate to high anti-diabetic and anti-oxidant effects. Geum kokanicum roots showed the highest α-glucosidase inhibition activity (91.0%±1.7) at the concentration of 500 µg/mL and DPPH radical scavenging potential (IC50: 11.6±0.5 μg/mL). Conclusion: The results demonstrated in-vitro anti-diabetic property of G. kokanicum, so detailed investigation to isolate the active compounds is suggested.

Introduction: Intravesical Mycobacterium Bovis bacillus Calmette-Guérin (BCG) therapy for non-muscle invasive bladder cancer has been successfully applied to prevent metastasis and disease progression. However, some studies have reported a percentage of treatment failure and recurrence along with possible side effects. Therefore, this study has evaluated the effect of administration of synthetic (SSeNPs) and biogenic selenium nanoparticles (BSeNPs) as an adjuvant drug in combination with intravesical BCG for the treatment of mice-bearing bladder tumors. Methods: Orthotopic bladder cancer model mice were established by 12 weeks of N-butyl-N-(4-hydroxybutyl) nitrosamine oral gavage. Mice-bearing bladder cancer was treated by sequential intravesical treatments with SSeNPs, BCG, BCG/SSeNPs, and BCG/SSeNPs. After immunotherapy, the status of the immune system was evaluated by quantitatively measuring mRNA expression of cytokines by Real-time qRT-PCR in the spleen samples and measuring cytokines protein level by enzyme-linked immunosorbent assay in the serum samples. As well, in the tumor microenvironment, the mRNA expression level of autophagic molecules (Beclin-1, ATG2B, and ATG5), apoptotic molecule (Caspase-3), iNOS, HMGB1, and PD-L1 were evaluated in all groups. Results: Immunotherapy with BCG/SSeNPs and BCG/BSeNPs elicited a considerable immune response by increasing the expression of IFN-γ, IL-12, and IL-6 and inhibiting the expression of IL-10 and TGF-β cytokines. As well, BCG/SSeNPs and BCG/BSeNPs could increase Caspase-3 expression and decrease autophagic genes as well as PD-L1. Conclusion: Our results showed that synthetic and biogenic SeNPs as an effective adjuvant could enhance intravesical BCG's efficacy and therapeutic effect for bladder cancer treatment with almost the same function.

Abstract In this work, new derivatives of biphenyl pyrazole-benzofuran hybrids were designed, synthesized and evaluated in vitro through enzymatic assay for inhibitory effect against α-glucosidase activity. Newly identified inhibitors were found to be four to eighteen folds more active with IC50 values in the range of 40.6 ± 0.2–164.3 ± 1.8 µM, as compared to the standard drug acarbose (IC50 = 750.0 ± 10.0 μM). Limited Structure-activity relationship was established. A kinetic binding study indicated that most active compound 8e acted as the competitive inhibitors of α-glucosidase with K i = 38 μM. Molecular docking has also been performed to find the interaction modes responsible for the desired inhibitory activity. As expected, all pharmacophoric features, used in the design of the hybrid, are involved in the interaction with the active site of the enzyme. In addition, molecular dynamic simulations showed compound 8e oriented vertically into the active site from mouth to the bottom and stabilized the enzyme domains by interacting with the interface of domain A and domain B and the back side of the active site while acarbose formed non-binding interaction with the residue belong to the domain A of the enzyme.

Abstract In an attempt to find novel, potent α-glucosidase inhibitors, a library of poly-substituted 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines 3a–ag have been synthesized through heating a mixture of 2-aminobenzimidazoles 1 and α-azidochalcone 2 under the mild conditions. This efficient, facile protocol has been resulted into the desirable compounds with a wide substrate scope in good to excellent yields. Afterwards, their inhibitory activities against yeast α-glucosidase enzyme were investigated. Showing IC50 values ranging from 16.4 ± 0.36 µM to 297.0 ± 1.2 µM confirmed their excellent potency to inhibit α-glucosidase which encouraged us to perform further studies on α-glucosidase enzymes obtained from rat as a mammal source. Among various synthesized 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines, compound 3k exhibited the highest potency against both Saccharomyces cerevisiae α-glucosidase (IC50 = 16.4 ± 0.36 μM) and rat small intestine α-glucosidase (IC50 = 45.0 ± 8.2 μM). Moreover, the role of amine moiety on the observed activity was studied through substituting with chlorine and hydrogen resulted into a considerable deterioration on the inhibitory activity. Kinetic study and molecular docking study have confirmed the in-vitro results.

In the last three decades, biological products have gradually developed to be an essential basis in the pharmaceutical industry. Advancements in this field have encouraged the frontiers of science to bring life-saving treatments to patients suffering from incurable diseases, such as cancers and has also assisted clinicians in managing chronic diseases e.g., rheumatoid arthritis.

Noscapine is an antispasmodic alkaloid used as antitussive and anti-cough obtained from plants in the Papaveraceae family which this benzylisoquinoline alkaloid and its synthetic subsidiaries (called noscapinoids) are being assessed for their anticancer potential. The present research aimed to investigate the induction of DNA destruction and viability of HepG2 tumor spheroid culture influenced by noscapine and nanosuspension of noscapine. Culture of HepG2 cells as spheroids was treated with different concentrations of noscapine for 24 h on Day 11. Afterward, viability assay and alkaline comet assay methods were applied to examine the viability and induced DNA destruction, respectively. Based on the results, no significant impact was observed from Tween 40 on the viability and DNA damage levels in comparison with the control (p > 0.05). Moreover, increasing noscapine concentration resulted in a dose-dependent reduction in viability of hepatic cancer cells and elevation of DNA damages, showing a correlation between rises of DNA damages and viability decline.

Background and objectives: Dracocephalum species are mentioned in Iranian traditional medicine for enhancement of cognitive performance. In the present study, the acetyl cholinesterase inhibitory and butyryl cholinesterase inhibitory activities as well as the anti-oxidant and anti-tyrosinase effects of three Iranian Dracocephalum species (D. kotschyi, D. multicaule, D. polychaetum was analyzed). Methods: The extractions were performed stepwise with hexane, chloroform, ethyl acetate (EtOAC), methanol (MeOH) and water. AChE and BChE inhibitory properties were measured by a microplate assay. Total phenolic content of all extracts were also evaluated and anti-oxidant activities of the extracts were assessed using DPPH, FRAP assays. Tyrosinase inhibitory activity was measured using the modified dopachrome method with L-DOPA as the substrate. Results: The results showed that the EtOAc extract of D. multicaule and MeOH extract of D. kotschyi were the most active anti-oxidant and anti-tyrosinase extracts which showed the highest amounts of phenolic compounds. Dracocephalum multicaule demonstrated the most considerable activity in AChE inhibition and D. polychaetum the highest activity in BChE inhibition. The aqueous extract of D. multicaule inhibited both AChE and BChE. Conclusion: Dracocephalum multicaule can be suggested as a proper natural candidate for improvement of cognitive disorders.

Molecular interactions are crucial between the enzyme molecules and the surrounding solution in an enzymatic catalysis. Although aqueous solutions used as conventional enzymatic reaction media, non-aqueous enzymology emerges as a major area of biotechnology research and development. Ionic liquids, as new generation of promising alternatives to traditional organic solvents, possess potential industrial enzymatic applications. Enzymes in ionic liquids present enhanced activity, stability, and selectivity. In addition, the potential of ionic liquids in bio-catalysis is raised by high ability of dissolving a wide variety of substrates and their extensively tunable solvent properties through appropriate modification of the cations and anions. However, despite the bio-friendly nature of ionic liquids for enzymatic reactions, their growing interests increase concerns associated with toxicity and environmental pollution of such compounds. This mini-review presents a brief highlight of the contemporary knowledge of enzymes activity and stability in ionic liquids and the environmental influences regarding the potential risks related to the growing applications of these green solvents. HIGHLIGHTS •Conventional organic solvents can be replaced by ionic liquids as green solvents. •Ionic liquids are used as additives, catalysts, or reaction media in industries. •Advantages and disadvantages of ionic liquids are discussed. •Potential environmental hazards linked to application of ionic liquids are highlighted. •The environmental fate needs to be considered in designing safer ionic liquids.

Despite the progress in treatment of infectious diseases, ability of microorganisms to develop the resistance to routine antibiotics has still remained as a big global challenge in clinics. This subject matter keeps the infections top in the list of life threatening diseases especially in those individuals suffering from nosocomial infections. The importance of this global health challenge urges researchers to find an alternative solution with more efficacies to treat infections. There are some alternative approaches by which the global spread of resistant bacteria could be controlled. Through these ways, using bacteriophages instead of different generation of antibiotics brings many promises. According to results of different studies using bacteriophages in the management of infectious disease especially in nosocomial infections not only helps to reduce the spread of antibiotics resistance but also raises the hopes for the rescue of the suffering patients. Bacteriophages can open a new therapeutic window in the control and the treatment of the infectious disease with better efficacy. HIGHLIGHTS •Bacteriophage can be used as an antimicrobial agent for treatment of bacterial infection. •Bacterial resistance to routine antibiotics is a big challenge in the world. •Specificity toward bacteria is one of the important characteristic of phages.

Lipases are the biocatalysts with outstanding prospects in industry and medicine. They have proven to be useful in various hydrolytic and synthetic reactions. However, there are some limitations for impure lipases that may restrict their widely uses in industrial applications. Purification is sometimes vital for the characterization of the function, structure, and interactions of lipases. The lipase immobilization is also an efficient strategy for increasing the enzyme activity and stability, and getting a simpler recovery. Lipases are naturally produced together with many other proteins that they may occupy some surface of immobilization solid support and decrease the final activity. The coupling of immobilization and purification of lipase will overcome the mentioned problems and obtain the maximum purification yields. The present mini-review will discuss the use of the techniques that permit to join immobilization and purification of lipases in a single step, including control of the immobilization conditions by interfacial activation on hydrophobic supports, the development of specific supports with affinity for lipases, and the use of bio-affinity supports including immuno- and lectin affinity HIGHLIGHTS •Lipases are the biocatalysts with outstanding prospects in industry and medicine. •Simultaneous immobilization-purification may enhance lipase activity and stability. •Lipases have a mechanism of interfacial activation in the presence of hydrophobic interfaces. •The lipase immobilization on hydrophobic supports is a much-utilized strategy. •Bio-affinity is a promising approach to increase lipase final yield and activity.

Stereo-selectivity is an important feature in the development of the synthesis of biologically active organic compounds. In this process, (bio) catalysts exhibit substrate specificity that allows high levels of chemo- and regio-selectivity. Over the past decade, several peptides have been developed as effective bio-catalysts for a range of synthetically valuable reactions. In comparison with proteins owing a large number of amino acids and high molecular weights, peptide-catalysts possess only a few amino acid residues, which may adopt a secondary structure suitable for synthesis of desired chiral products. In addition, the flexible nature of peptides consents for tuning of reactivity and selectivity by replacing amino acid residues. These unique aspects provide attractive biocatalysts platform for asymmetric syntheses. Highlights • Asymmetric catalysis has an impressive progression in the manufacture of pharmaceuticals. • Enzymes and natural/synthetic peptides are attractive biocatalysts of the chiral reactions. • Peptides show unique features compared with other catalysts in asymmetric catalysis.

Purpose: PLGA nanoparticles (NPs) have been extensively investigated as carriers of different drug molecules to enhance their therapeutic effects or preserve them from the aqueous environment. Streptokinase (SK) is an important medicine for thrombotic diseases. Methods: In this study, we used electrospray to encapsulate SK in PLGA NPs and evaluate its activity. This is the first paper which investigates activity of an electrosprayed enzyme. Effect of three input parameters, namely, voltage, internal diameter of needle (nozzle) and concentration ratio of polymer to protein on size and size distribution (SD) of NPs was evaluated using artificial neural networks (ANNs). Optimizing the SD has been rarely reported so far in electrospray. Results: From the results, to obtain lowest size of nanoparticles, ratio of polymer/enzyme and needle internal diameter (ID) should be low. Also, minimum SD was obtainable at high values of voltage. The optimum preparation had mean (SD) size, encapsulation efficiency and loading capacity of 37 (12) nm, 90% and 8.2%, respectively. Nearly, 20% of SK was released in the first 30 minutes, followed by cumulative release of 41% during 72 h. Activity of the enzyme was also checked 30 min after preparation and 19.2% activity was shown. Conclusion: Our study showed that electrospraying could be an interesting approach to encapsulate proteins/enzymes in polymeric nanoparticles. However, further works are required to assure maintaining the activity of the enzyme/protein after electrospray.

Nanoparticles have comprehensively affected various sights of human life. Through the wide range of claims about nanosized particles and their functions, biomedical applications are of much interest among health care researchers due to the nanoparticles' potential for use in the process of disease diagnosis, control and treatment. In this regard, inorganic nanoparticles, which have high potential in diagnostic and therapeutic systems, have recently received much attention in oncology. Although inorganic nanoparticles initially seemed an appropriate tool for cancer imaging and diagnosis, their ability to attack cancerous cells as anticancer drugs or carriers in other drugs has also demonstrated promising results. The present review primarily provides a brief survey of various studies in which metal nanoparticles such as gold, silver, iron oxide, and metalloid nanoparticles viz. tellurium and bismuth were exploited for therapeutic or diagnostic purposes in oncology. Then the application of selenium nanoparticles as a therapeutic agent against cancer in in vitro and in vivo studies is reviewed in detail. Although inorganic nanoparticles seem to be useful tools for cancer imaging and diagnosis, their potential for attacking cancerous cells as anticancer substances or even carriers for anticancer medications should not be underestimated.

Background and Objectives: Serralysin is an extracellular metalloprotease from Serratia marcescens which has been the subject of extensive biological investigations. The goal of this study was to extract and purify serralysin from S. marcescens and to investigate its cytotoxic activity on the colorectal cancer cell line. Materials and Methods: The presence of the serralysin gene was confirmed using PCR. The supernatant of bacterial culture was collected and precipitated using ammonium sulfate. The precipitated protein was dialyzed and subjected to ion exchange chromatography for further purification. Casein assay and skim milk assay was used to confirm the enzymatic activity. SDS-PAGE was used to visualize the presence of serralysin. Metalloprotease inhibition activity was performed using 50 mM EDTA. Cytotoxic activity of serralysin was assessed on MTT assay. Results: The PCR product corresponding to serralysin was estimated to be approximately 1500 bp. A transparent zone around the bacterial colonies on skim milk agar and casein digestion confirmed the proteolytic activity of serralysin. A 52 kDa band in SDS-PAGE corresponding to serralysin was observed before and after purification processes. MTT assay showed IC50 values 24.78 μg/ml and 19.16 μg/ml after 24 h and 48 h exposure of Caco-2 cells to serralysin, respectively. Conclusion: Our results showed that native serralysin has anticancer potential and may be a candidate for further pharmaceutical research and development. Further in vivo and in vitro mechanistic studies are suggested to confirm the biological activities.

Various proteins and enzymes produced during algal photosynthesis can be used in economic development and environment management, such as in wastewater treatment, production of fine chemicals, and biodiesel production. This mini-review presents various enzymes isolated from algae and suggests that algae, given their unique properties, could be explored for large-scale production of enzymes as future biocatalyst factories. Highlights • Various proteins and enzymes are produced during algal photosynthesis. • Algae use phosphoglycolate phosphatase and glycolate oxidase as metabolizing enzymes. • Algae possess the ability to produce commercial enzymes. • Out of the 10,000 algae species, only a few are cultivated on an industrial scale. • Algal wastes can be manipulated and recycled for production of various enzymes.

As a chronic inflammatory disease, atherosclerosis is responsible for thousands of deaths worldwide each year, and it imposes massive economic costs on individuals and on society. Because of its high importance, the discovery of sensitive and accurate strategies for imaging, targeted drug delivery, and therapeutic monitoring of this condition is essential. In recent years, continuous research has achieved remarkable successes in the use of nanotechnology in the molecular imaging and treatment of atherosclerosis. Among various nanoparticles — such as metallic, polymeric, and lipid — metallic nanoparticles are being considered due to their unique properties for use in treatment and imaging. It should be taken into consideration that some of the metal nanoparticles themselves can cause adverse biological effects, and these effects should be considered important risk factors in the pathological pathways leading up to atherosclerosis. This review provides a description of the applications and potential toxicity of metal nanoparticles in atherosclerosis.

Alginate-gelatin mixed gel was applied to immobilized laccase for decolorization of some synthetic dyes including crystal violet. The immobilization procedure was accomplished by adding alginate to a gelatin solution containing the enzyme and the subsequent dropwise addition of the mixture into a stirred CaCl2 solution. The obtained data showed that both immobilized and free enzymes acted optimally at 50°C for removal of crystal violet, but the entrapped enzyme showed higher thermal stability compared to the free enzyme. The immobilized enzyme represented optimum decolorization at pH 8. Reusability of the entrapped laccase was also studied and the results showed that ca. 85% activity was retained after five successive cycles. The best removal condition was applied for decolorization of seven other synthetic dyes. Results showed that the maximum and minimum dye removal was related to amido black 10B and eosin, respectively.