Solvent-free synthesis, biological evaluation and in silico studies of novel 2-amino-7-(bis(2-hydroxyethyl)amino)-4H-chromene-3-carbonitrile derivatives as potential a-amylase inhibitors

Abstract

Despite a wide range of kinase inhibitory activities exhibited by 2-amino-4H-chromenes, their potential application towards α-amylase inhibition remained rarely explored to date. For that purpose, a series of new 2-amino-7-(bis(2-hydroxyethyl)amino)-4(phenyl)-4H-chromene-3-carbonitrile derivatives has been synthesized via piperidine catalyzed solvent-free protocol and evaluated for their antidiabetic activity as potential α-amylase inhibitors. The dose-dependent in vitro α-amylase inhibition study revealed that, most of these compounds exhibited significant antidiabetic activity having more than 50 % α-amylase inhibition at the dose of 10 µg/mL. Among these, compound 5b was more potent than acarbose with 91 % inhibition of α-amylase and IC50 of 3.60 ± 0.01 µg/mL. Enzyme kinetic studies to estimate mode of inhibition showed that inhibition of α-amylase by compound 5b was competitive type with a Ki value of 0.97 µg/mL. Further, in silico studies of targeted compounds reinforced the results being involved in favorable binding interactions within the active site of α-amylase. Moreover, the in silico predicted properties of compound 5b regarded as a non-toxic and safer antidiabetic agent.