Dihydroquinazolin-4(1H)-one derivatives as novel and potential leads for diabetic management

A variety of dihydroquinazolin-4(1H)-one derivatives (1-37) were synthesized via "one-pot" three-component reaction scheme by treating aniline and different aromatic aldehydes with isatoic anhydride in the presence of acetic acid. Chemical structures of compounds were deduced by different spectroscopic techniques including EI-MS, HREI-MS, H-1-, and C-13-NMR. Compounds were subjected to alpha-amylase and alpha-glucosidase inhibitory activities. A number of derivatives exhibited significant to moderate inhibition potential against alpha-amylase (IC50 = 23.33 +/- 0.02-88.65 +/- 0.23 mu M) and alpha-glucosidase (IC50 = 25.01 +/- 0.12-89.99 +/- 0.09 mu M) enzymes, respectively. Results were compared with the standard acarbose (IC50 = 17.08 +/- 0.07 mu M for alpha-amylase and IC50 = 17.67 +/- 0.09 mu M for alpha-glucosidase). Structure-activity relationship (SAR) was rationalized by analyzing the substituents effects on inhibitory potential. Kinetic studies were implemented to find the mode of inhibition by compounds which revealed competitive inhibition for alpha-amylase and non-competitive inhibition for alpha-glucosidase. However, in silico study identified several important binding interactions of ligands (synthetic analogues) with the active site of both enzymes.