Α-glucosidase Enzyme Inhibition Research Articles

Peptide conjugates of 18β-glycyrrhetinic acid as potent inhibitors of α-glucosidase and AGEs-induced oxidation

18β-Glycyrrhetinic acid (18β-GA) is known for several biological activities, and has been the focus of extensive research for the development of therapeutic agents. In the current study, 18β-GA-peptide conjugates 2-11 were evaluated for their in vitro α-glucosidase inhibitory and antiglycation activities. Structure-activity relationship (SAR) established and molecular interactions of active bioconjugates with the enzyme's binding sites were predicted through molecular modeling approach. In tripeptide moiety of conjugates 2−11, peptide residue at position 1 was found to have a significant role on α-glucosidase inhibition. The most active 18β-GA-peptide conjugates 5 (18β-GA-Cys1-Tyr2-Gly3), and 8 (18β-GA-Pro1-Tyr2-Gly3) exhibited several-fold potent α-glucosidase inhibition (IC50 values 20–28 μM), as compared to standard drug acarbose (IC50 = 875.8 ± 2.10 µM). Kinetic studies of potent compounds, 4–8 revealed that conjugate 5 exhibits competitive-type of inhibition, while conjugates 6–8 showed a non-competitive type of inhibition. The simulation studies also supported the kinetic results that conjugate 5 (18β-GA-Cys1-Tyr2-Gly3) inhibits the α-glucosidase enzyme by blocking its substrate binding site. AGEs-induced NO• inhibitors play an important role in controlling the inflammation associated with diabetes mellitus. The peptide conjugates 2–11 were also evaluated in vitro for AGEs-induced NO• inhibition using RAW 264.7 macrophage cell line. Our data revealed that conjugates 7–10 were the more potent AGEs-induced NO• inhibitors, comparable to standards rutin, and PDTC. The peptide conjugate 5 (a competitive inhibitor of α-glucosidase) also exhibited a strong inhibitory activity against AGEs-induced NO• production. Furthermore, peptide conjugates 2–11 were found non-cytotoxic to mouse fibroblast NIH-3T3, and murine macrophages RAW 264.7 cell lines. In conclusion, our data demonstrates that besides possessing strong α-glucosidase inhibition, the newly synthesized peptide conjugates also alleviated the AGEs-induced NO• production in RAW macrophages. Dual inhibition of α-glucosidase enzyme, and AGEs-induced NO• production by 18β-GA-peptide conjugates qualify them for further research in anti-diabetic drug discovery.

Computational Analysis of Plant-Derived Terpenes as α -glucosidase Inhibitors for the Discovery of Therapeutic Agents against Type 2 Diabetes Mellitus

The hyperglycemic condition due to diabetes could be managed through retardation of the carbohydrate metabolism by inhibiting the enzymes involved in its degradation. Currently available therapeutic drugs for diabetes as inhibitors of α-glucosidase have limitations on safety, efficacy, and potency. Terpenes have been traditionally used for the treatment of different ailments in humans. Pharmacological activities related to different types of terpenes include antiviral, anticancer, antidepressant, anti-inflammatory, and antidiabetic among others. This study is aimed to unravel the novel antidiabetic plant-derived terpenes as α-glucosidase inhibitors and to investigate the molecular mechanisms underlying this activity. To determine the binding affinity of the plant-derived terpenes with the α-glucosidase target enzyme, an in-house library of 86 terpenes was created after a thorough search of the literature. The terpenes were virtually screened against the receptor protein by performing molecular docking via MOE software package. The binding affinity of the selected compounds was confirmed through molecular dynamic simulation studies. Further, pharmacophore studies, drug-likeness, and ADMET analysis of the top scoring terpenes were also performed. The docking score, drug-likeness assessment, pharmacokinetics analysis, and pharmacophore studies revealed that three compounds namely Gypsogenin -O-α-D-galactopyranosyl-(1-6)-β-D-glucopyranosyl-(1-6)-[β-D-glucopyranosyl-(1-3)]-β-D-glucopyranosyl ester, Segetalic acid and 22-α hydroxychiisanoside are effective inhibitors of α-glucosidase enzyme compared to the standard inhibitors. These findings showed that plant derived terpenes are potential α-glucosidase inhibitors and need to be explored through modern techniques for the development of effective plant-based antidiabetic drugs.

Synthesis of 1,2,3,triazole modified analogues of hydrochlorothiazide via click chemistry approach and in-vitro α-glucosidase enzyme inhibition studies.

The current study was aimed to discover potent inhibitors of α-glucosidase enzyme. A 25 membered library of new 1,2,3-triazole derivatives of hydrochlorothiazide (1) (HCTZ, a diuretic drug also being used for the treatment of high blood pressure) was synthesized through click chemistry approach. The structures of all derivatives 2-26 were deduced by MS, IR, 1H-NMR, and 13C-NMR spectroscopic techniques. All the compounds were found to be new. Compounds 1-26 were evaluated for α-glucosidase enzyme inhibition activity. Among them, 18 compounds showed potent inhibitory activity against α-glucosidase with IC50 values between 24 and 379µM. α-Glucosidase inhibitor drug acarbose (IC50 = 875.75 ± 2.08μM) was used as the standard. Kinetics studies of compounds 6, 9, 11, 12, 15, 20, 23, and 24 revealed that only compound 15 as a mixed-type of inhibitor, while others were non-competitive inhibitors of α-glucosidase enzyme. All the compounds were found to be non-cytotoxic when checked against mouse fibroblast 3T3 cell line.

Understanding the bioaccessibility, α-amylase and α-glucosidase enzyme inhibition kinetics of Allmania nodiflora (L.) R.Br. ex Wight polyphenols during in vitro simulated digestion

This study renewed focus on Allmania nodiflora, a green leafy vegetable with diverse nutritional and medicinal properties. The bioaccessibility and the impact of in vitro simulated digestion on polyphenolics were investigated and identified using LC-MS. Although in vitro digestion reduced polyphenolics, the pancreatic digested sample showed a significant bioaccessibility of 97% with better metal ion binding activity (99%). Increased α-amylase and α-glucosidase inhibition (>45%) potentials were also observed in the digested samples. The presence of compounds such as rutin, caffeic acid, catechin, saikosaponin was also identified to be responsible for the enzyme inhibition against postprandial hyperglycemia. These results indicated that the pH of the digestive buffers is responsible for the structural changes in polyphenols for assimilation in the intestine. Hence, A. nodiflora leaf could serve as a functional food having higher assimilated polyphenolics with abundant therapeutic potential, which would be indispensible for future nutraceutical product development from green leafy vegetables.

Synthesis, crystal structure, spectroscopic characterization, α-glucosidase inhibition and computational studies of (E)-5-methyl-N′-(pyridin-2-ylmethylene)-1H-pyrazole-3-carbohydrazide

A new crystal, i.e, (E)-5-methyl-N′-(pyridin-2-ylmethylene)-1H-pyrazole-3-carbohydrazide (E-MPPC) has been synthesized and characterized by using FT-IR, UV-Vis, 1H-NMR, 13C-NMR, ESI-MS and single-crystal X-ray diffraction. In addition, a density functional theory study for the title compound was carried out. The theoretical geometry of the ground state and the electronic structure of the title compound were optimized by the DFT/B3LYP method in conjunction with 6-311++G(d,p) basis set. E-MPPC was evaluated in vitro for their α-glucosidase enzyme inhibition. The title compound displayed moderate inhibitory activity with IC50 value of 714.25 ± 8.33 µM against α-glucosidase enzyme. In addition, molecular docking study was performed to investigate how E-MPPC interacts with the protein structure of α-glucosidase enzyme. Final intermolecular energy and estimated inhibition constant for this docking study were obtained as -5.50 kcal/mol and 173.57 µM, respectively. The first order static hyperpolarizability (β) parameter for E-MPPC was also calculated as 11.2×10−30 esu. Natural bond orbital analysis was also executed to investigate intramolecular charge transfer interactions in the title compound.

Aroma Profile and α-Glucosidase Inhibitory Activity of Essential Oil of Mentha spicata Leaves

Mentha spicata Linn. abundantly growing in the Kurdistan Region, and traditionally used as a flavouring agent in foods, and medicinally utilized in the treatment of stomach discomfort specifically in dyspepsia and indigestion, also used in the treatment of a common cold. The present study aims to characterize the aroma profile of essential oil obtained from leaves of M. spicata, and also determine its α-glucosidase inhibitory activity in an in-vitro model. The aroma profile of essential oil was determined by gas-chromatography mass spectroscopy (GC/ MS), and the analysis resulted in the identification of twenty-nine constituents in the essential oil of M. spicata leaves. Menthol (32.81 %), carvone (19.67 %), 1,8-cineol (15.62 %), isomenthone (7.14 %), neomenthol (6.71 %), and β-pinene (3.39 %) were found as major chemical compounds in the essential oil of M. spicata leaves. The essential oil of M. spicata produces concentration-dependent inhibition of α-glucosidase enzyme with IC50 value 681.19±16.81 μg/mL. The present study successfully explores the aroma profile of M. spicata essential oil, and in-vitro α-glucosidase assay provides a scientific basis for its possible use in the treatment of diabetes.

Linking the Phytochemicals and the α-Glucosidase and α-Amylase Enzyme Inhibitory Effects of Nigella sativa Seed Extracts.

Nigella sativa L. (Ranunculaceae), commonly referred to as black seeds or black cumin, is used in popular medicine (herbal) all over the world for the treatment and prevention of several diseases, including diabetes. This study aims to investigate the inhibitory effect of N. sativa extracts and fractions against the activities of intestinal α-glucosidase and pancreatic α-amylase in vitro, and to explain the inhibitory effect of these fractions against these enzymes by identifying their active compounds responsible for this effect and determine their modes of inhibition. To do so, N. sativa hexane and acetone extracts were prepared and analyzed by GC–MS and HPLC–DAD, respectively. The hexane extract was further fractioned into eight different fractions, while the acetone extract generated eleven fractions. The extracts as well as the resulting fractions were characterized and evaluated for their potential in vitro antidiabetic activity using intestinal α-glucosidase and pancreatic α-amylase inhibitory assays in vitro. Hexane extract and fractions were less active than acetone extract and fractions. In the case of intestinal α-glucosidase activity, the acetone fraction SA3 had a high inhibitory effect on intestinal α-glucosidase activity with 72.26 ± 1.42%, comparable to the effect of acarbose (70.90 ± 1.12%). For the pancreatic α-amylase enzymatic inhibitory assay, the acetone fractions showed an inhibitory capacity close to that for acarbose. In particular, the SA2 fraction had an inhibitory effect of 67.70 ± 0.58% and was rich in apigenin and gallic acid. From these fractions, apigenin, (−)-catechin, and gallic acid were further characterized for their inhibitory actions. IC50 and inhibition mode were determined by analyzing enzyme kinetic parameters and by molecular modeling. Interestingly, (−)-catechin showed a possible synergistic effect with acarbose toward α-glucosidase enzyme inhibition, whereas apigenin showed an additive effect with acarbose toward α-amylase enzymatic inhibition. Furthermore, we studied the toxicity of N. sativa hexane and acetone extracts as well as that of acetone fractions. The result of acute toxicity evaluation demonstrated that N. sativa extracts were nontoxic up to a concentration of 10 g/kg, except for fraction SA3. Taken together, these results indicate that N. sativa extracts and/or derived compounds could constitute promising nutraceuticals for the prevention and treatment of type 2 diabetes mellitus.

Design, Synthesis and Bioactivity Investigation of Novel 2,3-Diarylthiazolidine-4-Ones as Potent α-Glucosidase Inhibitors

Herein, we have designed and synthesized sixteen novel 2,3-diarylthiazolidin-4-one derivatives 6a-p and tested their activity as α-Glucosidase inhibitors. Target compounds 6a-p were characterized using spectroscopic methods (1H-NMR, 13C-NMR, MS, IR), elemental analysis, and melting point. α-Glucosidase inhibition activity was evaluated using the α-Glucosidase enzyme inhibition kit. All 6a-p showed higher α-Glucosidase inhibition activity (90 to 704 µM) in comparison to acarbose as a standard (IC50: 750 µM). 6p, 6m, and 6f exerted the best activity with the IC50 value of 90, 100, and 149 µM respectively. Enzyme kinetic studies showed a competitive mode of inhibition for the most active compound, 6p; molecular docking study revealed the mode of interactions between the most active compounds and enzyme active site. To evaluate the cytotoxicity profile of the synthesized compounds, an MTT assay was done on three different cell lines which showed all 6a-p are safe and nontoxic with IC50 values higher than 750 µM.

Chemical Composition, α-Glucosidase Inhibitory and Anticancer Activity of Essential Oil of Thymus vulgaris Leaves

Dietary herbs are used for imparting flavour, aroma, and piquancy to foods. Besides their role in improving food quality, spices also have health benefits, such as anticancer, antidiabetic, antimicrobial, antioxidant, hypolipidemic, analgesic, immunostimulant, etc. Thymus vulgaris (family: Lamiaceae) is a valuable medicinal herb known for its health benefits. The essential oil from T. vulgaris was isolated by the hydrodistillation method, and chemical constituents in it were determined by GC-MS. Anticancer activity was determined using a DNA ladder assay, and antidiabetic activity was accessed by α-glucosidase inhibition. The GC-MS analysis showed the presence of 16 chemical constituents, and thymol (55.88 %), linalool (13.71 %), carvacrol (8.36 %), and p-cymene (6.00 %) were found as major components. The antidiabetic activity of T. vulgaris essential oil showed potent inhibition of α-glucosidase enzyme with an IC50 value 125.1±4.25 μg/mL. The anticancer activity results revealed that treating MCF-7 cells with 100 μg/mL essential oil of thyme produces DNA fragmentation and promotes apoptosis. The current study provides a scientific basis for its possible use in controlling diabetes and breast cancer. The study further expands the knowledge of T. vulgaris chemical composition and provides evidence of ethnomedicinal use of the plant by exploring antidiabetic and anticancer activities.

Chemical Characterization and Antidiabetic Activity of Essential Oils from Pelargonium graveolens Leaves

Pelargonium graveolens (Geranium) is a source of the finest quality of fragrance and its essential oils are used as antibacterial, and antifungal agents. The aim of the current research is to determine chemical constituents in the essential oil of P. graveolens by GC-MS and evaluate its antidiabetic activity via α-glucosidase inhibition assay. The chemical composition of P. graveolens essential oil was determined by GC/MS and its antidiabetic activity was assessed through inhibition of α-glucosidase enzyme in in-vitro models. GC-MS analysis determines 36 chemical components in the essential oil of P. graveolens leaves, and citronellyl isovalerate (10.41 %), menthol (9.61 %), linalool (8.63 %), p-menthone (6.31 %), and geranyl tiglate (4.99 %) were recorded as major constituents. The essential oil of P. graveolens leaves showed concentration dependant inhibition of α-glucosidase enzyme ranging from 28.13±1.41 to 74.24±2.53 µg/mL for concentration ranging from 31.25 to 1000 µg/mL. The IC50 values for of P. graveolens and acarbose were found as 93.72±4.76 and 80.4±2.17 µg/mL, respectively against the α-glucosidase enzyme. The study finding explores the chemical components of P. graveolens growing in the Iraqi Kurdistan region and scientifically supported its possible use in diabetic patients for controlling postprandial hyperglycemia.

Imidazole Appended Novel Phenoxyquinolines as New Inhibitors of α-Amylase and α-Glucosidase Evidenced with Molecular Docking Studies

In the process of a search for new compounds to reduce hyperglycemia by α-amylase and α-glucosidase enzyme inhibition, a series of imidazole appended phenoxyquinoline derivatives were synthesized. Initially, 2-cholo-3-formyl quinoline 3 was treated with various substituted phenol in the presence of K2CO3 in DMF to get 2-phenoxyquinoline-3-carbaldehyde which in turn was treated with o-phenylenediamine to afford the corresponding 3-(1H-benzo[d]imidazol-2-yl)-2-phenoxyquinolines (7a–j). All the synthesized compounds were evaluated for their in vitro and in silico α-amylase and α-glucosidase inhibitory activity using acarbose as a standard. Among the tested compounds, compound 7a was found to exhibit a potent binding affinity; and inhibitory activity (80.90% and 76.26%) with corresponding IC50 values of 104.30 ± 3.31 μmol/mL and 135.67 ± 2.80 μmol/mL toward α-amylase and α-glucosidase, respectively.

GC/MS Profile and In-Vitro α-Glucosidase Inhibitory Activity of Essential Oil of Eucalyptus camaldulensis Dehnh Collected from (Erbil) Iraq

Background: Eucalyptus camaldulensis Dehnh is abundantly found in Erbil, Iraq and commonly used as an antispasmodic and antipyretic remedy for treating respiratory tract diseases. The present study aimed to evaluate the effectiveness of E. camaldulensis in achieving glucose homeostasis through the inhibition of α-glucosidase enzyme using in-vitro model and also determine the chemical composition of essential oil by gas chromatography mass spectroscopy (GC/MS). Methods: The chemical composition of E. camaldulensis essential oil by was determined by GC/MS and its antidiabetic activity was assessed through inhibition of α-glucosidase enzyme in in- -vitro models. Results: The essential oil yielded 40 chemical constituents amounting to 98.55%. The major constituents of essential oil of E. camaldulensis leaf were 1,8-cineole (28.4%), isocaryophyllene oxide (8.4%), β-ocimene (7.9%), α-farnesene (7.9%), globulol (7.3%), terpinen-4-ol (7.6%), isophytol (3.6%), viridiflorol (3.2%), p-cymen-3-ol (3.1%) and α-bisabolol (1.2%). The essential oil of E. camaldulensis showed concentration-dependent inhibition of α-glucosidase enzyme and the inhibition ranged from 75.38±2.09 to 6.08±1.89% for concentration 100 to 3.125 μg/mL. The α-glucosidase inhibition of E. camaldulensis (IC50 value 16.7±2.61 μg/mL) was found almost comparable with standard drug acarbose (IC50 value 12.04±3.17 μg/mL). Conclusion: The result of this study concluded E. camaldulensis essential oil as having 1,8-cineole, isocaryophyllene oxide and β-ocimene as major constituents; the study findings also confirm the traditional claim of its use in the treatment of diabetes mellitus.

3,6-dimethyl ester-α-mangostin Compound Modified from Isolate α-mangostin Garcinia Mangostana Linn

Isolate α-mangostin (1) is a phenolic compound derived from oxygenated and prenylated xanthones and major compounds obtained from the fruit peel of G. mangostana Linn., Which is stated to have inhibitory activity against α-glucosidase enzymes, serves to determine the antidiabetic activity resulting in IC50 value of 29,92 µM, is of the nature moderate to positive control (acarbose) with an IC50 value of 4.55 µM. A modified compound of α-mangostin (1) with acetic anhydride obtained by 3,6-di-methyl ester-α-mangostin (2) derivative showed the inhibitory value of α-glucosidase (IC50 13,89 μM), this value is better than the activity inhibition of α-mangostin (1), but not as active as the positive control value of the acarbose compound. The separation process to obtain α-mangostin isolates from the fruit peel of G. mangostana Linn was obtained by maceration method with ethyl acetate solvent, followed by refraction using a vacuum liquid chromatography (KCV) method over silica gel (Merck 60 G) and eluted using eluent (n-hexane: ethyl acetate) with increasing polarity, to produce as much pure crystal (21.66 g), yield (24%). While the structural characterization of the two compounds was carried out using UV-Vis, IR, HRESIMS, 1H-NMR and 13C-NMR spectroscopic methods, the antidiabetic testing was carried out using the α-glucosidase enzyme inhibition method.

Cyclic Polyketides with α-Glucosidase Inhibitory Activity from Endiandra kingiana Gamble and Molecular Docking Study

A phytochemical investigation of the methanolic extract of Endiandra kingiana (bark) led to the isolation of four major compounds which are kingianic acid A (1), tsangibeilin B (2), kingianin A (3) and kingianin F (4). The structures were determined by 1D- and 2D-NMR analysis in combination with HRMS experiments. The compounds were screened for their in vitro α-glucosidase inhibition activity. Among them, compounds 3-4 showed potent α-glucosidase inhibition activity with IC50 value at 11.9 ± 2.0 µM and 19.7 ± 1.5 µM, respectively. The molecular docking study found that both compounds were bound into the active site of the N-terminal of MGAM, and thus agreed with the in vitro α-glucosidase enzyme inhibition activity results.

Chemical Characterization and α-Glucosidase Inhibitory Activity of Essential Oil of Lavandula angustifolia Flowers

Lavandula angustifolia is a major source of high-quality fragrance and extensively used in aromatherapy. Lavender is widely found in the Jammu and Kashmir region of India. The aim of the present study to determine chemical constituents present in the essential oil of L. angustifolia flowers by gas chromatography-mass spectrometry and to evaluate its antihyperglycemic activity via inhibition of the α-glucosidase enzyme. The chemical constituents of the essential of L. angustifolia flowers were determined by gas chromatography-mass spectrometry and its antihyperglycemic activity was evaluated by inhibition of the α-glucosidase enzyme. The Lavender flowers yielded 41 chemical constituents which constitute about 99.28 % of total essential oil and the major chemical constituents include linalyl acetate (39.28 %), linalool (26.76 %), trans-β-caryophyllene (4.77 %), lavandulyl acetate (3.04 %) and 1,8-cineole (2.15 %). The essential oil from flowers of L. angustifolia showed concentration dependant α-glucosidase enzyme inhibition that varies from 24.27±2.18 to 64.04±1.29 % for concentration 31.25 to 1000 μg/mL, respectively. The L. angustifolia essential oil with IC50 value 609.44±13.01 was found comparable with acarbose (IC50 value 526.5±12.19 μg/mL) against the α-glucosidase enzyme. The study finding provides the basis for the possible use of L. angustifolia essential oil in the management of postprandial hyperglycemia in diabetic patients.

Chemical characterization, antidiabetic and anticancer activities of Santolina chamaecyparissus.

Santolina chamaecyparissus is an important medicinal plant growing in the Mediterranean region and has been reported as a potent anti-inflammatory, antibacterial, antioxidant, and antifungal agent. The purpose of the current research is to identify the chemical constituents in ethyl acetate extract (EAE) from the leaves of S. chamaecyparissus, and to evaluate antidiabetic, and anticancer activity. Chemical constituents of EAE were identified by GC-MS, and the antidiabetic activity was evaluated by α-glucosidase inhibition assay. The anticancer activity was assessed by Epidermal Growth Factor Receptor (EGFR) expression in human breast cancer cell line (MCF7) by using quantitative RT-PCR method. GC-MS analysis of EAE of S. chamaecyparissus yielded 44 compounds. Tetrapentacontane (27.15%), eicosyl acetate (8.40%), 2-methylhexacosane (6.87%), and n-pentadecanol (5.44%) were found as major chemical constituents. The EAE of S. chamaecyparissus showed concentration dependant inhibition of α-glucosidase enzyme and the IC50 value (IC50 110 ± 4.25 µg/mL) was found comparable with standard acarbose (IC50 105 ± 3.74 µg/mL). The real-time qRT-PCR results showed that the EGFR protein (bcl-2) in human breast cancer cell line (MCF7) was negatively expressed with a value of −0.69297105 after treatment with EAE (100 µg/mL). The study results are suggesting the possible use of S. chamaecyparissus in the management of diabetes, and human breast cancer.

Evaluation and docking of indole sulfonamide as a potent inhibitor of α-glucosidase enzyme in streptozotocin –induced diabetic albino wistar rats

We have synthesized new hybrid class of indole bearing sulfonamide scaffolds (1–17) as α-glucosidase inhibitors. All scaffolds were found to be active except scaffold 17 and exhibited IC50 values ranging from 1.60 to 51.20 µM in comparison with standard acarbose (IC50 = 42.45 µM). Among the synthesized hybrid class scaffolds 16 was the most potent analogue with IC50 value 1.60 μM, showing many folds better potency as compared to standard acarbose. Whereas, synthesized scaffolds 1–15 showed good α-glucosidase inhibitory potential. Based on α-glucosidase inhibitory effect, Scaffold 16 was chosen due to highest activity in vitro for further evaluation of antidiabetic activity in Streptozotocin induced diabetic rats. The Scaffold 16 exhibited significant antidiabetic activity. All analogues were characterized through 1H, 13CNMR and HR MS. Structure-activity relationship of synthesized analogues was established and confirmed through molecular docking study.

<strong>Antidiabetic and antioxidant potential of <em>Durio zibethinus</em> Murr. leaves ethanolic extract</strong>

Durio zibethinus Murr., commonly called Durian, though well known for its rich medicinal uses, only fewer studies are available on the leaves of this plant. In this study, we investigated the antioxidant and antidiabetic potential of ethanol extract of D. zibethinus leaves (DZL) from Malaysian geographical origin. DZL was subjected to the preliminary phytochemical screening along with the quantitative analysis of phenols and flavonoids. The in vitro antioxidant properties were evaluated by DPPH and ABTS methods and in vitro antidiabetic properties were evaluated by α-amylase and α-glucosidase enzyme inhibition studies. The results of the above biological activities were expressed as inhibitory concentration 50% for DZL and standard drugs (acarbose and ascorbic acid). Based on the acute oral toxicity test, two test doses (100 and 200 mg/kg) of DZL were compared with glibenclamide (5 mg/kg) for their effect on fasting blood glucose at various time intervals (0 to12 h) in glucose-loaded normoglycemic rats. DZL (200 mg/kg) showed a better response in streptozotocin (STZ) induced diabetic rats. The antioxidant assay of DZL showed an appreciable extract inhibitory concentration 50% against the free radicals generated by DPPH (1.61±0.07 μg/ mL) and ABTS (1.47±0.07 μg/mL) assays. Similarly, the in vitro antidiabetic assay results demonstrated a dose-dependent inhibition of α-amylase (2.58±0.08 μg/mL) and α-glucosidase enzymes (2.41±0.08 μg/ mL) by DZL. Both glucose-loaded normoglycemic rats and STZ-induced diabetic rats treated with DZL (200 mg/kg) exhibited a significant post-dose reduction in blood glucose levels ( P <0.01, 8 h and P <0.001, 12 h) when compared to normal and diabetic control rats, respectively. These findings suggest that the presence of polyphenols in DZL might be responsible for antioxidant and antidiabetic properties and DZL could be a natural source as an herbal remedy for diabetes.

Novel α-amylase and α-glucosidase inhibitors from selected Nigerian antidiabetic plants: an in silico approach

This study aimed to identify novel α-amylase and α-glucosidase inhibitors from Nigerian antidiabetic plants through in silico approach. Virtual screening of the 93 phytoconstituents was performed, and their inhibitory potentials were ranked based on their docking scores. Five hit molecules were selected for each enzyme target with their hydrogen bonding, hydrophobic, electrostatic, and pi interactions analyzed with discovery studio visualizer. The drug-likeness and ADMET studies of the hit molecules were performed to ascertain their druggability properties. Further, three top-ranked hit molecules were subjected to molecular dynamics simulations. The virtual screening, drug-likeness property, and ADMET studies, and molecular dynamics simulations carried out reveal Newbouldiaquinone A, Foetidin, Chamuvaritin, Cajaflavanone, and Azadirolic acid as potential inhibitors of α-amylase while Chamuvaritin, Newbouldiaquinone A, Flowerone, Scoparic acid A and Nimonol were potential inhibitors of α-glucosidase enzyme. Communicated by Ramaswamy H. Sarma

Synthesis, in vitro, and in silico studies of newly functionalized quinazolinone analogs for the identification of potent α-glucosidase inhibitors

Functionalized quinazolinone derivatives 1–30 were synthesized by two-step reaction. First, anthranilic acid was treated with substituted phenyl isothiocyanate to synthesize 3-aryl-2-thioxo-2,3-dihydroquinazolinone derivatives 1–8 which in turn reacted with different bromoacetophenone derivatives to obtain fully functionalized quinazolinone derivatives 9–30. Both reactions were catalyzed by triethylamine. All the products were characterized by EI-, HREI-MS, 1H-, and 13CNMR spectroscopic techniques. All compounds were subjected to their in vitro α-glucosidase inhibitory activity. Results showed that except compound 1–3, 5, 7, and 22, all compounds were found potent and showed many folds increased α-glucosidase enzyme inhibition as compared to standard acarbose (IC50 = 750.0 ± 10.0 µM). Compound 13 (IC50 = 85.0 ± 0.5 µM) was recognized as the most potent analog of the whole series, with ninefold enhanced inhibitory potential than the standard acarbose. Compounds 1–9, 11, 12, 22, and 26 were structurally known compounds, while remaining all are new. Kinetic study on compound 13 showed that the compound is following a competitive-type inhibition mechanism. Furthermore, in silico studies have also been performed to better rationalize the interactions between synthetic compound and active site of the enzyme.