3-Benzyl(phenethyl)-2-thioxobenzo[ g ]quinazolines as a new class of potent α-glucosidase inhibitors: synthesis and molecular docking study

摘要

Aim: Using a simple modification on a previously reported synthetic route, 3-benzyl(phenethyl)-2-thioxobenzo[ g ]quinazolin-4(3 H )-ones ( 1 and 2 ) were synthesized with high yields. Further transformation of 1 and 2 produced derivatives 3 - 26 , which were structurally characterized based on NMR and MS data, and their in vitro α-glucosidase inhibitory activity was evaluated using Baker's yeast α-glucosidase enzyme. Results: Compounds 2 , 4 , 8 , 12 and 20 exhibited the highest activity (IC_(50)?= 69.20, 59.60,?49.40, 50.20?and 83.20?μM, respectively) compared with the standard acarbose (IC_(50)?=?143.54?μM). Conclusion: A new class of potent α-glucosidase inhibitors was identified, and the molecular docking predicted plausible binding interaction of the targets in the binding pocket of α-glucosidase and rationalized the structure–activity relationship (SARs) of the target compounds.