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

Abstract

Diabetes 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.