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

Aim: Using a simple modification on a previously reported synthetic route, 3-benzyl(phenethyl)-2-thioxobenzo[g]quinazolin-4(3H)-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.