In vitro α–Glucosidase Inhibition, Cytotoxicity, SAR, Swiss ADME Prediction and Molecular Docking Study of New N–Substituted Hydantoin Derivatives

Abstract

AbstractDiabetes is a chronic metabolic disorder affecting about 463 million people globally. α‐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 α‐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 α‐glucosidase inhibition at 10, 50 and 100 μM. However, at 200 μM, 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 α‐glucosidase. The results correlated well with those of the experimental, thereby contributing towards the development of new α‐glucosidase inhibitors.