De novo drug design and biological evaluation of coumarin–pyrimidine co-drug derivatives as diabetic inhibitors: expanding a multi-algorithm approach with the integration of machine learning in pharmaceutical research†

Abstract

Optimization of hit compounds was carried out using the density functional theory. We introduce the coumarin-based co-drug by linkages (amide and oxime) of coumarins with pyrimidines to improve the pharmacokinetic activity of coumarin owing to the synergic effect of both collectively. Pharmacokinetic studies, including drug likeness, were performed using SWISSADMET, and toxicity was identified using a web-based server. Screened lead molecule W₆ (C) was synthesized and characterized by NMR spectroscopy, and its anti-diabetic activity was evaluated by in vitro α-amylase inhibition. This study identified W₆ as an active, new and more effective candidate for diabetes in drug discovery.