Effective Α-glucosidase Inhibitors Research Articles

Indenoquinoxaline-phenylacrylohydrazide hybrids as promising drug candidates for the treatment of type 2 diabetes: In vitro and in silico evaluation of enzyme inhibition and antioxidant activity

Existing drugs that are being used to treat type-2 diabetes mellitus are associated with several side effects; thus, exploring potential drug candidates is still an utter need these days. Hybrids of indenoquinoxaline and hydrazide have never been explored as antidiabetic agents. In this study, a series of new indenoquinoxaline-phenylacrylohydrazide hybrids (1−30) were synthesized, structurally characterized, and evaluated for α-amylase and α-glucosidase inhibitory activities, as well as for their antioxidant properties. All scaffolds exhibited varying degrees of inhibitory activity against both enzymes, with IC50 values ranging from 2.34 to 61.12 μM for α-amylase and 0.42 to 54.72 μM for α-glucosidase. Particularly, compounds 10, 16, 17, 18, 24, and 25 demonstrated the highest efficacy in inhibiting α-amylase, while compounds 6, 7, 8, 10, 12, 14, 13, 16, 17, 18, 24, and 25 were the most effective α-glucosidase inhibitors, compared to standard acarbose. Moreover, most of these compounds displayed substantial antioxidant potential compared to standard butylated hydroxytoluene (BHT). Kinetics studies revealed competitive inhibition modes by compounds. Furthermore, a comprehensive in silico study and toxicity prediction were also conducted, further validating these analogs as potential drug candidates. The structured compounds demonstrated enhanced profiles, underscoring their potential as primary candidates in drug discovery.

Hydrolysates of hemp (Cannabis sativa L.) seed meal: Characterization and their inhibitory effect on α-glucosidase activity and glucose transport in Caco-2 cells

Due to the lack of high value-added products and the rough utilization of hemp protein, which has the effect of regulating blood glucose, as well as the adverse effects of glucose-lowering drugs currently on the market, it is urgent to develop new safe and effective α-glucosidase inhibitors as substitutes for existing hypoglycemic drugs. Therefore, this study explored the physical and chemical properties, antioxidant activity, and inhibitory mechanism of α-glucosidase activity of non-dehulled hemp seed meal hydrolysate prepared by controlled enzymatic hydrolysis technology, as well as its inhibitory of α-glucosidase and glucose transmembrane transport in Caco-2 cells. Kinetic experiments indicated that the inhibition of α-glucosidase by hemp seed meal hydrolysate was reversible mixed inhibition. Cell experiments revealed that the hydrolysate inhibited both intracellular disaccharidase and the transport of glucose at different concentrations. In conclusion, the hemp seed meal hydrolysate can inhibit the activity of α-glucosidase and has potential value and application prospects in hypoglycemic effect.

Extraction of polyphenols from Potentilla fruticosa L. as α-glucosidase inhibitors

ABSTRACT This study utilized column chromatography and nuclear magnetic resonance (NMR) to isolate and identify 42 compounds in Potentilla fruticosa L. (PL), which compound 10 and 35 were preliminarily identified. Compounds 5–9, 11–13, 16, 17, 20, 23, 24 and 28 (total 14 polyphenols) promoted glucose consumption in IEC cells, exhibiting potential in reducing blood glucose levels. Mechanistic analysis revealed that the 14 polyphenols significantly inhibited α-glucosidase activity, and (expressed as semi-inhibitory concentration values) the capacity ranking is 13 > 9 > 12 > 5 > 16 > 8 > 17 > 7 > 6 > 11 > 28 > 23 > 24 > 20. Molecular docking showed that all 14 polyphenols have an active binding site with α-glucosidase, and the binding energy is all lower than −6.0 kcal·mol−1, thereby inhibiting the entry of p-nitrophenyl-d-glucoside. The results show that PL polyphenols can be used as effective α-glucosidase inhibitors.

α-Glucosidase Inhibitors Based on Oleanolic Acid for the Treatment of Immunometabolic Disorders

Using oleanolic acid as a starting compound, a series of new oleanane-type triterpenic derivatives were synthesized via O-acylation (with nicotinic, isonicotinic, and methoxycinnamic acid acyl chlorides), N-amidation (with cyclic- or polyamines), the Mannich reaction (with secondary cyclic amines), and Claisen–Schmidt condensation (with aromatic aldehydes), and their potencies as treatments for immunometabolic disorders were investigated. The compounds were evaluated against α-glucosidase and PTP1B enzymes and LPS-stimulated murine macrophages. It was found that the target compounds are highly effective α-glucosidase inhibitors but lack activity against PTP1B. A leading compound, N-methylpiperazine methylated 2,3-indolo-oleanolic propargyl amide 15, is also a micromolar inhibitor of NO synthesis in LPS-stimulated macrophages and suppresses oxidative bursts in neutrophils with similar efficiency. These results, in addition to its ability to stimulate glucose uptake in rat fibroblasts and improve maltose tolerance in rats, allow us to consider compound 15 a promising prototype drug for the treatment of immunometabolic defects in type 2 diabetes.

Coumarin linked thiazole derivatives as potential α-glucosidase inhibitors to treat diabetes mellitus.

Diabetes is a leading cause of kidney failure, blindness, heart attacks and lower limb amputation. Prevalence of diabetes is rising globally. α-glucosidase is validated target for controlling hyperglycemia because of its role in catalysing hydrolysis of carbohydrates to glucose in GIT. In an attempt to find novel safe and effective α-glucosidase inhibitors, coumarin linked thiazole was identified as potential scaffold on the basis of its interactions with the active site of α-glucosidase studied in silico. A series of coumarin linked thiazole derivatives were synthesized and analyzed for α-glucosidase inhibitory potential in an in-vitro assay. The synthesized molecules showed potent inhibition of α-glucosidase with IC50 values ranging from 0.14 to 9.38μM. The most potent compound 2-[(4-bromophenyl) amino)-N-(4- (2-oxo-2H-chromen-3-yl) thiazol-2-yl] acetamide was further docked with α-glucosidase and molecular dynamics studies were carried out for 100ns which suggested the stability of protein and ligand in the protein active site over the simulation period and role of hydrophobic interactions slightly more than the electrostatic/polar interactions in ligand- receptor stability. In summary, our results demonstrate efficacy of coumarin-linked thiazole as potential leads for further optimization and development.

Optimization of Extraction Process of Polysaccharides MAP-2 from Opuntia Milpa Alta by Response Surface Methodology and Evaluation of Its Potential as α-Glucosidase Inhibitor.

The α-glucosidase inhibitors play an important role in blood glucose control in patients with type 2 diabetes. At present, the development of new α-glucosidase inhibitors is an urgent clinical need. Our previous studies have found that the polysaccharide MAP-2 in the cactus Opuntia Milpa Alta has significantly better activity than acarbose (one of the most widely used first-line α-glucosidase inhibitors in clinical practice), but its optimal extraction process parameters and inhibition kinetic characteristics are not clear, and whether it has the potential to become a new α-glucosidase inhibitors is also unclear. In this study, based on previous research, we used the combination of single factor experiments and the response surface method (RSM) to identify the optimal extraction conditions for MAP-2 as follows: solid-liquid ratio 1:4, extraction temperature 90 °C, extraction time 1 h. Under these conditions, the extraction yield of MAP-2 was 3.47 ± 0.062%. When the concentration of MAP-2 was 16 mg/mL, the inhibition rate of α-glucosidase was 91.13 ± 0.62%. In addition, the results of inhibition kinetics showed that the inhibition rate of MAP-2 on α-glucosidase was the highest at pH 7.4 for 30 min, and showed a good dose-effect relationship, which was a reversible competitive inhibition. Meanwhile, we also compared the activities of MAP-2 and acarbose on the side effects of acarbose related enzymes. Compared with acarbose, MAP-2 not only had a better activation effect on lactase, but also inhibited the activity of hyaluronidase, and the activation and inhibition rate were positively correlated with the concentration. However, under the same conditions, the effect of acarbose on hyaluronidase was opposite to that of MAP-2. At low concentration, acarbose had a certain activation effect on lactase, but gradually attained an inhibitory effect with the increase in concentration. In contrast, MAP-2 not only activates lactase activity, improves diarrhea, abdominal distension, and abdominal pain, but also inhibits hyaluronidase activity, to solve the side effects of allergic reactions, suggesting that MAP-2 has the potential to become a novel and effective inhibitor of α-glucosidase with fewer side effects.

Effect of Ganoderma lucidum fermentation on the content and α-glucosidase inhibitory activity of mulberry leaves flavonoid

Diabetes is now a worldwide disease that has a negative impact on human health.As a result,the search for low-cost,safe,and effective diabetes treatment drugs derived from natural medicinal plants has become a research priority.Mulberry leaf(ML)flavonoids have been proven to be a highly effective α-glucosidase inhibitor and have a good effect on the treatment of diabetes.The solid state fermentation of Ganoderma lucidum utilizing ML as substrate was explored in this study with the goal of increasing the concentration and-glucosidase inhibitory effect of mulberry leaf flavonoid(MLF).The results indicated that fermented by G.lucidum for 8 d could increase the content of MLF from 1.596 mg/ml to 4.736 mg/ml.Meanwhile the polysaccharide in ML would be degraded and utilized as nutritions to support the cell growth of G.lucidum.The inhibitory rate of MLF on α-glucosidase was significantly enhanced by fermentation.During the concentration of 10μg/ml,the α-glucosidase inhibition rate of MLF was enhanced from 45.31±2.24%to 73.46±3.28%when fermented by G.lucidum for 8d.Moreover,it was found that the inhibition type of MLF would change from competitive inhibition to mixed-type inhibition.This study will serve as a reference for microbial fermentation and enrichment of medicinal plant active components,as well as a contribution to the high-value-added use of mulberry leaf resources.

Polycyclic Phenol Derivatives from the Leaves of Spermacoce latifolia and Their Antibacterial and α-Glucosidase Inhibitory Activity

Three new polycyclic phenol derivatives, 2-acetyl-4-hydroxy-6H-furo [2,3-g]chromen-6-one (1), 2-(1′,2′-dihydroxypropan-2′-yl)-4-hydroxy-6H-furo [2,3-g][1]benzopyran-6-one (2) and 3,8,10-trihydroxy-4,9-dimethoxy-6H-benzo[c]chromen-6-one (8), along with seven known ones (3–7, 9 and 10) were isolated for the first time from the leaves of Spermacoce latifolia. Their structures were determined by spectroscopic analysis and comparison with literature-reported data. These compounds were tested for their in vitro antibacterial activity against four Gram-(+) bacteria: Staphyloccocus aureus (SA), methicillin-resistant Staphylococcus aureus (MRSA), Bacillus cereus (BC), Bacillus subtilis (BS), and the Gram-(−) bacterium Escherichia coli. Compounds 1, 2, 5 and 8 showed antibacterial activity toward SA, BC and BS with MIC values ranging from 7.8 to 62.5 µg/mL, but they were inactive to MRSA. Compound 4 not only showed the best antibacterial activity against SA, BC and BS, but it further displayed significant antibacterial activity against MRSA (MIC 1.95 µg/mL) even stronger than vancomycin (MIC 3.9 µg/mL). No compounds showed inhibitory activity toward E. coli. Further bioassay indicated that compounds 1, 4, 5, 6, 8 and 9 showed in vitro α-glucosidase inhibitory activity, among which compound 9 displayed the best α-glucosidase inhibitory activity with IC50 value (0.026 mM) about 15-fold stronger than the reference compound acarbose (IC50 0.408 mM). These results suggested that compounds 4, 8 and 9 were potentially highly valuable compounds worthy of consideration to be further developed as an effective anti-MRSA agent or effective α-glucosidase inhibitors, respectively. In addition, the obtained data also supported that S. latifolia was rich in structurally diverse bioactive compounds worthy of further investigation, at least in searching for potential antibiotics and α-glucosidase inhibitors.

The novel homologue of the human α-glucosidase inhibited by the non-germinated and germinated quinoa protein hydrolysates after in vitro gastrointestinal digestion.

Quinoa (Chenopodium quinoa Willd) is a potential source of protein with ideal amino acid profiles which its bioactive compounds can be improved during germination and gastrointestinal digestion. The present investigation studies the impact of germination for 24hr and simulated gastrointestinal digestion on α-glucosidase inhibitory activity of the quinoa protein and bioactive peptides against the novel homologue of human α-glucosidase, PersiAlpha-GL1. The sprouted quinoa after gastroduodenal digestion was the most effective α-glucosidase inhibitor showing 81.10% α-glucosidase inhibition at concentration 4mg/ml with the half inhibition rate (IC50 ) of 0.07mg/ml. Based on the kinetic analysis, both the germinated and non-germinated samples before and after digestion were competitive-type inhibitors of α-glucosidase. Results of this study showed the improved α-glucosidase inhibitory activity of the quinoa bioactive peptides after germination and gastrointestinal digestion and highlighted the potential of metagenome-derived PersiAlpha-GL1 as a novel homologue of the human α-glucosidase for developing the future anti-diabetic drugs. PRACTICAL APPLICATIONS: This study aimed to evaluate the effect of germination and gastrointestinal digestion of the quinoa protein and bioactive peptides on α-glucosidase inhibitory activity against the novel PersiAlpha-GL1. Metagenomic data were used to identify the novel α-glucosidase structurally and functionally homologue of human intestinal. The results showed the highest inhibition on PersiAlpha-GL1 by a germinated quinoa after gastroduodenal digestion and confirmed the potential of PersiAlpha-GL1 to enhance theeffectivenessof the anti-diabetic drugs for industrial application.

Utilization of Cassava Wastewater for Low-Cost Production of Prodigiosin via Serratia marcescens TNU01 Fermentation and Its Novel Potent α-Glucosidase Inhibitory Effect.

The purpose of this study was to reuse cassava wastewater (CW) for scaled-up production, via the fermentation of prodigiosin (PG), and to conduct an evaluation of its bioactivities. PG was produced at the yield of high 6150 mg/L in a 14 L-bioreactor system, when the designed novel medium (7 L), containing CW and supplemented with 0.25% casein, 0.05% MgSO4, and 0.1% K2HPO4, was fermented with Serratia marcescens TNU01 at 28 °C in 8 h. The PG produced and purified in this study was assayed for some medical effects and showed moderate antioxidant, high anti-NO (anti-nitric oxide), and potential α-glucosidase inhibitory activities. Notably, PG was first reported as a novel effective α-glucosidase inhibitor with a low IC50 value of 0.0183 µg/mL. The commercial anti-diabetic drug acarbose was tested for comparison and had a lesser effect with a high IC50 value of 328.4 µg/mL, respectively. In a docking study, the cation form of PG (cation-PG) was found to bind to the enzyme α-glucosidase by interacting with two prominent amino acids, ASP568 and PHE601, at the binding site on the target enzyme, creating six linkages and showing a better binding energy score (−14.6 kcal/mol) than acarbose (−10.5 kcal/mol). The results of this work suggest that cassava wastewater can serve as a low-cost raw material for the effective production of PG, a potential antidiabetic drug candidate.

Comparative study of inhibition mechanisms of structurally different flavonoid compounds on α-glucosidase and synergistic effect with acarbose

Flavonoid compounds have anti-diabetic activity, which can control blood glucose levels by inhibiting α-glucosidase activity. In this paper, the inhibition mechanisms between four flavonoid compounds and α-glucosidase were studied by multispectroscopic methods and molecular docking. The results showed that the inhibitory activities of flavonoid compounds were higher than that of acarbose, and the sequence of inhibition effect was scutellarein > nepetin > apigenin > hispidulin > acarbose. Also, the synergistic effects of flavonoid compounds combined with acarbose on inhibiting α-glucosidase activity were observed. The fluorescence results showed that flavonoid compounds combined with α-glucosidase to form a stable complex. And the spectral analysis indicated that the microenvironmental and secondary structure of α-glucosidase were changed. The present study demonstrated that the molecular structure of flavonoid compounds played an important role in the inhibition process, namely, scutellarein with more hydroxyl groups on the A-ring might serve as the most effective α-glucosidase inhibitor.

Effects of Ganoderma lucidum fermentation on the main chemical components in mulberry leaves and the inhibition of α-glucosidase

Mulberry leaves have been used in the clinical treatment of diabetes since ancient times. A variety of bioactive components in mulberry leaf extract are effective α-glucosidase inhibitors. Though much research has been done on dry mulberry leaves, few have been done on the fresh mulberry leaves. In this study, Ganoderma lucidum was used to ferment fresh mulberry leaves, the effects of microbial fermentation on the content of active components and α-glucosidase inhibitory activity in dry and fresh mulberry leaves were measured. The results showed that, compared with dry mulberry leaves, fresh mulberry leaves were more suitable for the growth of Ganoderma lucidum. The nutrition needed for the growth of Ganoderma lucidum was mainly from the degradation of polysaccharides in fresh mulberry leaves. After fermentation, the polysaccharides content of fresh mulberry leaves decreased from 224.18 mg/g to 22.08 mg/g. The enrichment of bioactive components in fresh mulberry leaves was higher than that in dry mulberry leaves. The contents of flavonoids and alkaloids in fresh mulberry leaves were increased by 34% and 35% respectively compared with nonfermented mulberry leaves. The inhibitory effect of flavonoids and alkaloids on α-glucosidase of fresh mulberry leaves was significantly enhanced by fermentation. In conclusion, the fermentation of fresh mulberry leaves by Ganoderma lucidum fungus can not only enrich the content of α-glucosidase inhibitors in mulberry leaves, but also significantly improve their inhibitory activity.

Enhance the flavonoids content and α-glucosidase inhibitor efficiency of mulberry leaves by fermented with Ganoderma lucidum

Diabetes is a kind of chronic disease that seriously threatens human health. α-glucosidase inhibitors are an effective way to inhibit the increase of postprandial blood glucose. Mulberry leaf flavonoids can be used as highly effective α-glucosidase inhibitors, but usually in low concentrations. Microbial fermentation is an effective method to increase the content of flavonoids in plants. In this paper, the fermentation of mulberry leaves with Ganoderma lucidum was conducted to investigate the cell growth of microbial, the content and α-glucosidase inhibitory efficiency of flavonoids in mulberry leaves. The results indicated that mulberry leaves can satisfy the nutritional needs of G. lucidum, and the maximum cell dry weight of 393.32 mg was obtained after a 10 d of fermentation. The flavonoid content in mulberry leaves was increased significantly with the fermentation time. Compared to unfermented mulberry leaves, the flavonoid content in mulberry leaves fermented for 8 d increased by 56.5%. The inhibitory efficiency of the fermented flavonoids was also significantly improved. The IC50 of α-glucosidase of flavonoids extracted from 8 d fermented mulberry leaves and unfermented mulberry leaves were 0.041 mg/mL and 0.01 mg/mL, respectively. This article will provide a reference for the enrichment of functional active ingredients in plants through microbial fermentation technology.

Design, synthesis and α-glucosidase inhibition study of novel embelin derivatives

Embelin is a naturally occurring para-benzoquinone isolated from Embelia ribes (Burm. f.) of the Myrsinaceae family. It was first discovered to have potent inhibitory activity (IC50 = 4.2 μM) against α-glucosidase in this study. Then, four series of novel embelin derivatives were designed, prepared and evaluated in α-glucosidase inhibition assays. The results show that most of the embelin derivatives synthesised are effective α-glucosidase inhibitors, with IC50 values at the micromolar level, especially 10d, 12d, and 15d, the IC50 values of which are 1.8, 3.3, and 3.6 μM, respectively. Structure–activity relationship (SAR) studies suggest that hydroxyl groups in the 2/5-position of para-benzoquinone are very important, and long-chain substituents in the 3-position are highly preferred. Moreover, the inhibition mechanism and kinetics studies reveal that all of 10d, 12d, 15d, and embelin are reversible and mixed-type inhibitors. Furthermore, docking experiments were carried out to study the interactions between 10d and 15d with α-glucosidase.

3D-QSAR Analysis and Molecular Docking Studies on 3-Arylcoumarin Derivatives as Potential α- Glucosidase Inhibitors

α-glucosidase inhibitors (AGI) are the structural moieties that are found to be of utmost importance in the fields of pharmacy and which involves delaying the absorption of carbohydrates by blocking of alpha-glucosidase enzyme in the brush border of small intestine and plays an important role in constituting a promising therapeutic class against diabetic disease (Type II). In this study, the three-dimensional quantitative structure-activity relationship (3D-QSAR) and docking models were developed using Fujito-Ban analysis in VALSTAT software and Molegro Virtual Docker 6.0. The theoretical models were generated from 29 3-arylcoumarin inhibitors of α-glucosidase. A robust QSAR model with good prediction in internal and external verification was constructed, where r2 and q2 were 0.821 and 0.646 respectively. The QSAR study suggested that substitution of group at R1 position on 3-arylcoumarin ring with electron withdrawing group favourable for the anti-diabetic activity. Molecular docking studies were performed with the coordinates of the α-glucosidase crystal structure (PDB ID: 3WY2), as the results we found that the ligands would form the hydrogen bond interactions with Asp 202, Arg 400 and Glu 271 of the protein receptor generally. For better α-glucosidase inhibitory activity, dipole seems to give good results. These results of the QSAR analysis and molecular docking provided some useful information for designing new and effective α-glucosidase inhibitors in significance of stability and the binding interaction between ligand the receptor site by considering the validation parameters.

Butyrolactone-I, an efficient α-glucosidase inhibitor, improves type 2 diabetes with potent TNF-α-lowering properties through modulating gut microbiota in db/db mice.

The aim of this study was to evaluate the effects of butyrolactone-I (A6) on type 2 diabetes (T2D) in db/db mice because A6 was found to inhibit α-glucosidase activities and TNF-α release, which were associated with improving T2D. Male db/db mice were divided into 6 groups and given an equivalent volume of olive oil, acarbose, or different doses of A6 for 4 wk (n = 8/group). In this study, 11 butenolide derivatives were screened for their α-glucosidase and TNF-α suppressive activity in vitro. A6, an efficient α-glucosidase inhibitor, exerts hypoglycemic and multiple activities in reducing weight, improving glucose tolerance and insulin resistance, increasing short-chain fatty acid (SCFA) levels, activating SCFA-induced increases in glucagon-like peptide 1 and peroxisome proliferator-activated receptor-γ expression, enhancing intestinal mucosal barrier function and mitigating endoxemia in db/db mice. These effects may result from mediation of gut microbiota by A6. Meanwhile, A6, with potent TNF-α-lowering properties, was demonstrated to have multiple salutary effects with excellent structural stability and long-term safety in vivo. A6, an effective α-glucosidase inhibitor with high security and stability, exerted potent antidiabetic effects in vivo. Furthermore, the modulation of gut microbiota of A6 was demonstrated to be one of the mechanisms contributing to anti-inflammation properties and improving endoxemia. Our work confirms that the compound A6 is a prospective drug candidate for T2D.-Wu, W., Liu, L., Zhu, H., Sun, Y., Wu, Y., Liao, H., Gui, Y., Li, L., Liu, L., Sun, F., Lin, H. Butyrolactone-I, an efficient α-glucosidase inhibitor, improves type 2 diabetes with potent TNF-α-lowering properties through modulating gut microbiota in db/db mice.

Evaluation of Alpha Glucosidase Inhibitor (Miglitol) for its Efficacy in Constipation Associated with Diabetes

Abstract: Objectives: Recently, miglitol emerged as effective α-glucosidase inhibitor for the treatment of diabetic mellitus with specific advantages over currently available class of antidiabetic drugs. The aim of the present study was to evaluate the effects of miglitol in diabetes and associated constipation. Methods: Diabetes was induced in Wistar albino rat by streptozotocin given at dose of 25mg/kg, i.p. for 3 days consecutively to develop diabetes complications during next four weeks. The drugs were administered for 4 weeks starting from day 29 of post streptozotocin injections. Food and water intake, fecal parameters were measured on weekly basis. Gastrointestinal transit was monitored by charcoal meal and α- amylase activity was measured in all the treatment groups. Key findings: Treatment with miglitol demonstrated markedly increase in the gastrointestinal transit ratio in the diabetic rats and showed less α- amylase inhibitory activity, which providing evidences that miglitol does not exert constipation in the rats as compared to acarbose, which strongly inhibits the α- amylase enzyme and cause constipation in diabetic rats. Conclusion: These results suggest that miglitol has a potential to be used in the treatment of diabetes and associated constipation. Key words: Miglitol, Diabetes, Constipation, Gastrointestinal motility, α- amylase enzyme activity.

Pharmacophore studies of 1, 3, 4-oxadiazole nucleus: Lead compounds as α-glucosidase inhibitors

α-glucosidase inhibition is a rational approach in the effective management of type 2 diabetes. Several inhibitors of this enzyme class are in clinical use, but are riddled with efficacy, potency and safety challenges. For this reason, new effective α-glucosidase inhibitors are under investigation. Compounds with 1, 3, 4-oxadiazole nucleus have shown preclinical efficacy as α-glucosidase inhibitors and as anti-inflammatory agents. Moreover, 1, 3, 4-oxadiazoles also play important role in pesticide chemistry, polymer science, and they are considered as the building blocks in the production of new molecular agents for bioactive molecules. In the present study, computational analyses were carried out for various 1,3,4-oxadiazole (which were divided into BF2 & BF3 series); the most active compound was taken as a potent inhibitor, and pharmacophore were formed from that compound, followed by validation against a test database. The pharmacophore-based virtual screening was performed and, by successive eliminations, six compounds of different interactions with the significant amino acid residues were selected as the lead compounds. It is concluded that these six compounds with 1, 3, 4-oxadiazoles nucleus might be used as promising drug candidates in α-glucosidase inactivation and thus we recommend further in vitro and in vivo pharmacological and safety studies.

Polyoxomolybdates as α-glucosidase inhibitors: Kinetic and molecular modeling studies

Noninsulin dependent diabetes mellitus is a serious global disease that is treated by inhibiting α-glucosidase to reduce the glucose content in the blood. Several incompletely satisfactory therapeutic drugs are already on the market. In this report, we showed that polyoxomolybdates based on Keggin-type architecture are promising candidates. Kinetic studies indicate that H3PMo12O40, Na4PMo11VO40, Na6PMo11FeO40 and Na7PMo11CoO40 strongly inhibit α-glucosidase with IC50 values of 6.14 ± 0.38 μM, 52.33 ± 1.41 μM, 161.90 ± 7.68 μM and 103.10 ± 2.88 μM, respectively. Moreover, H3PMo12O40, Na4PMo11VO40, and Na7PMo11CoO40 are reversible, competitive inhibitors with KI values of 0.018 mM, 0.146 mM and 0.121 mM, respectively. Na6PMo11FeO40 inhibited α-glucosidase in a reversible noncompetitive manner with KI and KIS of 0.312 mM and 0.412 mM, respectively. Molecular docking simulation suggested that H3PMo12O40 binds into the substrate binding site in accordance with competitive inhibition behavior and offered, in addition, an initial insight into the polypeptide-inhibitor interactions. This work presents a promising new perspective for designing effective α-glucosidase inhibitors and further demonstrates the enormous potential of polyoxomolybdates as enzyme inhibitors.

Salvia elegans, Salvia greggii and Salvia officinalis Decoctions: Antioxidant Activities and Inhibition of Carbohydrate and Lipid Metabolic Enzymes.

Salvia elegans Vahl., Salvia greggii A. Gray, and Salvia officinalis L. decoctions were investigated for their health-benefit properties, in particular with respect to antioxidant activity and inhibitory ability towards key enzymes with impact in diabetes and obesity (α-glucosidase, α-amylase and pancreatic lipase). Additionally, the phenolic profiles of the three decoctions were determined and correlated with the beneficial properties. The S. elegans decoction was the most promising in regard to the antioxidant effects, namely in the scavenging capacity of the free radicals DPPH•, NO• and O2•–, and the ability to reduce Fe3+, as well as the most effective inhibitor of α-glucosidase (EC50 = 36.0 ± 2.7 μg/mL vs. EC50 = 345.3 ± 6.4 μg/mL and 71.2 ± 5.0 μg/mL for S. greggii and S. officinalis, respectively). This superior activity of the S. elegans decoction over those of S. greggii and S. officinalis was, overall, highly correlated with its richness in caffeic acid and derivatives. In turn, the S. officinalis decoction exhibited good inhibitory capacity against xanthine oxidase activity, a fact that could be associated with its high content of flavones, in particular the glycosidic forms of apigenin, scutellarein and luteolin.