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ID: ALA3872209

Journal: Eur J Med Chem

Title: Inhibitory activity evaluation and mechanistic studies of tetracyclic oxindole derivatives as α-glucosidase inhibitors.

Authors: Sun H, Zhang Y, Ding W, Zhao X, Song X, Wang D, Li Y, Han K, Yang Y, Ma Y, Wang R, Wang D, Yu P.

Abstract: α-Glucosidase inhibitors are known to prevent the digestion of carbohydrates and reduce the impact of carbohydrates on blood glucose. Three series of tetracyclic oxindole derivatives were designed, synthesized and evaluated for α-glucosidase inhibitory activity in vitro. Compound 6t exhibited the most potent inhibitory activity with IC50 0.7 μM and was about 170 times as active as acarbose (IC50 = 115.8 μM). The kinetic analysis of compound 6t revealed it inhibited α-glucosidase in an irreversible and mixed manner. Fluorescence spectra indicated that 6t directly bound to α-glucosidase. Docking simulation showed the existence of potential H-bonding, van der Waals, Pi and Sigma-Pi interactions between 6t and α-glucosidase.

CiteXplore: 27487567

DOI: 10.1016/j.ejmech.2016.07.044