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Diabetes mellitus is a chronic metabolic disorder with increasing prevalence and long-term complications. The aim of this study was to identify α-glucosidase inhibitory compounds with potential anti-hyperglycemic activity. For this purpose, a series of new clioquinol derivatives 2a-11a was synthesized, and characterized by various spectroscopic techniques. The enzyme inhibitory activities of the resulting derivatives were assessed using an in-vitro mechanism-based assay. All the tested compounds 2a-11a of the series showed a significant α-glucosidase inhibition with IC 50 values 43.86-325.81 µM, as compared to the standard drug acarbose 1C 50 : 875.75 ± 2.08 µM. Among them, compounds 4a, 5a, 10a, and 11a showed IC 50 values of 105.51 ± 2.41, 119.24 ± 2.37, 99.15 ± 2.06, and 43.86 ± 2.71 µM, respectively. Kinetic study of the active analogues showed competitive, non-competitive, and mixed-type inhibitions. Furthermore, the molecular docking study was performed to elucidate the binding interactions of most active analogues with the various sites of α-glucosidase enzyme. The results indicate that these compounds have the potential to be further studied as new anti-diabetic agents., (Copyright © 2021. Published by Elsevier Inc.)

Celebrex (1), commonly used as an anti-inflammatory drug, was functionalized (compounds 2-9) to identify new α-glucosidase inhibitors. Initially, all the synthesized derivatives were evaluated for anti-inflammatory activity but none was found to be active. Subsequently a random biological screening was carried out. Interestingly many of them were found to be potent α-glucosidase inhibitors in vitro. All the structures of synthesized derivatives were deduced through 1 H NMR, FAB-MS, HR-MS, FT-IR analysis. The single-crystal X-ray structures of compounds 1, and 5 further confirmed the assigned structures. Compounds exhibited a potent α-glucosidase inhibitory activity (IC 50  = 92.32 ± 1.530-445.20 ± 1.04 µM) against tested standard acarbose (IC 50  = 875.75 ± 2.08 µM), except compounds 2 and 4, which appeared as inactive. Among them, compound 9 (IC 50  = 92.32 ± 1.530 µM) was the most potent inhibitor of α-glucosidase enzyme. Molecular docking studies revealed that compounds 6, and 9 interacted with the key amino acid residues of α-glucosidase via H-bonding, and π-π stacking interactions. α-Glucosidase is a key target for the anti-diabetic drug development, and its inhibitors are known to exert anti hyperglycemic effect and help in lowering of post-prandial blood glucose levels., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In the present study, a series of new carbazole linked 1H-1,2,3-triazoles (2-27) were synthesized via click reaction of N-propargyl-9H-carbazole (1) and azides of appropriate acetophenones and heterocycles. Synthesized carbazole triazoles including 7, 9, 10, 19, 20, and 23-26 (IC 50 =0.8±0.01-100.8±3.6μM), exhibited several folds more potent α-glucosidase inhibitory in vitro activity as compared to standard drug, acarbose. Compounds 2-5, 7-13, and 17-27 did not show any cytotoxicity against 3T3 cell lines, except triazoles 6, and 14-16. Among the series, carbazole triazoles 23 (IC 50 =1.0±0.057μM) and 25 (IC 50 =0.8±0.01μM) were found to be most active, and could serve as an attractive building block in the search of new non-sugar derivatives as anti-diabetic agents., (Copyright © 2017 Elsevier Inc. All rights reserved.)

α‐Glucosidase inhibition is one of the key targets for controlling diabetes. In consideration of that, new L‐valinol derived fluorinated sultam triazoles were synthesized as α‐glucosidase inhibitors, and their activities were further compared with the precursor molecules (sulfonamides, sultams, and N‐propargyl sultams). Primarily, all the synthesized sultam triazoles and precursor compounds (sulfonamides, sultams, and N‐propargyl sultams) were evaluated for different biological activities, including cytotoxicity, anti‐inflammatory, and α‐glucosidase inhibitory activities. Results revealed that only sultam triazoles exhibited inhibition against α‐glucosidase enzyme (IC50 values: 173 to 194 μM) using acarbose (IC50: 875.85 ± 2.03 μM) as the standard drug. These sultam triazoles were prepared after few steps, starting from enantiopure L‐valinol, which differ electronically (due to the position of fluorine atom and different positions on aromatic ring). Structures of all the compounds were evaluated using different spectroscopic techniques. Kinetics of active compounds were also investigated to find their mode of inhibition. [ABSTRACT FROM AUTHOR]

[Display omitted] • A series of dibenzazepine-linked isoxazoles was prepared using Nitrile oxide-Alkyne cycloaddition reaction as potent α-glucosidase inhibitors, which may act as hits for drug design and discovery of new anti-diabetic compounds. • Most of the compounds showed potent inhibition against α-glucosidase enzyme (IC 50 = 35.62 ± 1.48 to 333.30 ± 1.67 µ M) using acarbose as a reference drug (IC 50 = 875.75 ± 2.08 µ M). • Enzyme kinetic studies and molecular docking studies of synthesized isoxazoles were performed to study the enzyme-inhibitor interactions. α -Glucosidase inhibition is a valid approach for controlling hyperglycemia in diabetes. In the current study, new molecules as a hybrid of isoxazole and dibenzazepine scaffolds were designed, based on their literature as antidiabetic agents. For this, a series of dibenzazepine-linked isoxazoles (33 – 54) was prepared using Nitrile oxide-Alkyne cycloaddition (NOAC) reaction, and evaluated for their α -glucosidase inhibitory activities to explore new hits for treatment of diabetes. Most of the compounds showed potent inhibitory potency against α -glucosidase (EC 3.2.1.20) enzyme (IC 50 = 35.62 ± 1.48 to 333.30 ± 1.67 µM) using acarbose as a reference drug (IC 50 = 875.75 ± 2.08 µM). Structure-activity relationship, kinetics and molecular docking studies of active isoxazoles were also determined to study enzyme-inhibitor interactions. Compounds 33 , 40 , 41 , 46 , 48 – 50 , and 54 showed binding interactions with critical amino acid residues of α -glucosidase enzyme, such as Lys156, Ser157, Asp242, and Gln353. [ABSTRACT FROM AUTHOR]