Abstract
Diabetes is a chronic metabolic disorder affecting about 463 million people globally. alpha-Glucosidase (EC.3.2.1.20) inhibitors are among the FDA-approved oral anti-diabetic medications used to treat type 2 diabetes. In search of new potential alpha-glucosidase inhibitors, fifteen of our previously synthesized hydantoin derivatives 8 a-o were evaluated for their antidiabetic activity. All compounds 8 a-o showed weak alpha-glucosidase inhibition at 10, 50 and 100 mu M. However, at 200 mu M, compound 8 o was the most potent among the series followed by compounds 8 a, 8 d, 8 l and 8 n exhibiting moderate inhibition. The established SAR depended upon the exchange of methyl with methoxy and dioxole derivatives at positions 3 and 4 of the phenyl ring. Cytotoxicity studies revealed that most of the compounds have no cytotoxic effect. Furthermore, Swiss ADME predictions of compounds 8 a, 8 d, 8 i, 8 l and 8 o showed high gastrointestinal intestinal absorption required for intestinal absorption of any drug. Most compounds did not obey drug-likeness character since they violated Ghose and Veber rules with MW>350 and rotors>11. Molecular docking was carried out to investigate the binding interaction of compounds with the active site of alpha-glucosidase. The results correlated well with those of the experimental, thereby contributing towards the development of new alpha-glucosidase inhibitors.