Green synthesis, ADME and docking studies, and in vitro assessment of chromone-based α -aminophosphonates as dual inhibitors of α -amylase and α -glucosidase

A novel series of chromone-based α-aminophosphonates (7a–j) as potential dual inhibitors of α-amylase and α-glucosidase were developed and synthesized using a solvent-free, ultrasonic-assisted Kabachnik-Fields reaction catalyzed by nano-ZnO, with high yields. Before synthesis, molecular docking simulations and in silico ADMET evaluation were used to estimate the pharmacokinetic properties and inhibitory interactions with α-amylase and α-glucosidase enzymes. Spectroscopy was utilized to determine structural integrity. The compounds were tested in vitro for inhibitory effects on two enzymes linked to type 2 diabetes. When compared to acarbose, the in silico ADME analysis showed favorable pharmacokinetic characteristics suggesting promising oral drug-likeness. Stronger binding affinities were found in molecular docking studies toward pancreatic α-amylase and α-glucosidase than acarbose. Compounds 7e, 7d, and 7i inhibited α-amylase and α-glucosidase with IC50 values comparable to or better than acarbose, suggesting their promise as scaffolds for anti-diabetic drug development.