Abstract
A novel series of benzylidene-quinazolinone hybrids 8(a,b) and 10(a-n) were designed, synthesized, and evaluated for their in vitro alpha-glucosidase inhibitory effect aiming to discover efficient anti-diabetic agents. The synthesized compounds were assessed for their in vivo anti-hyperglycemic activities against STZ-induced hyperglycemic rats. Five compounds (10(m), 10(f), 10(c), 10(d) and 8(b) ) demonstrated potent activities with percent reduction in blood glucose levels of 43.07, 40.14, 39.83, 37.04 and 36.16, respectively. The most active members were further evaluated in vitro for their alpha-glucosidase inhibitory binding affinities. Among them, Compound 10(m) containing 4-hydroxybenzylidene moiety and compound 10(f) with 4-chlorobenzylidene moiety connected to the acetohydrazide demonstrated the most potent inhibitory activities towards alpha-glucosidase with IC50 values of 561 and 610 mu M, respectively. Molecular docking study was performed in order to understand the molecular interactions between the molecule and enzyme. (C) 2021 Elsevier B.V. All rights reserved.