Synthesis, Docking and In-Vitro Studies of Quinazoline Derivatives as Dipeptidyl Peptidase-4 and Α-Amylase Inhibitors for Treating Diabetes

Abstract

The study involved condensation of 8-bromo-7-(but 2yn-1yl)-3-methyl-3,7-dihydro-1H-purine-2,6-dione with 2-(chloro methyl)-4-methyl quinazoline. The compound obtained was assigned 3, on which different substitutions were made at 8th position, to obtain various derivatives of quinazoline. The obtained derivatives were characterized using I.R, 1H-NMR, 13C-NMR and Mass spectra. For finding the diabetic activity of the synthesized compounds, they were subjected for their inhibitory activity on α-amylase, using Acarbose as standard and DPP-4 using Metformin as standard. The results obtained, from the activity performed was nearly equal with that of the standards used and synthesized compound 3C was found to possess inhibitory activity.  It has also been confirmed by docking studies, that Compound 3C and Metformin when docked on 3 proteins 2ONC, 5Y7J and 2OQV, Compound 3C was found to be most potent drug candidate against DPP-4.

Keywords: Quinazoline, Synthesis, In silico Docking, In vitro DPP-4, In vitro α-amylase, Antidiabetic activity.