Synthesis of novel thiosemicarbazone derivatives as antidiabetic agent with enzyme kinetic studies and antioxidant activity

Abstract

Novel thiosemicarbazone derivatives were synthesized via condensation reactions between the corresponding thiosemicarbazides and 4-(methylsulfonyl)acetophenone. The chemical structures of all compounds were elucidated by infrared (IR), 1H-NMR and 13C-NMR spectroscopy and mass spectrometry. Antioxidant studies of all compounds were performed by using CUPRAC, FRAP, DPPH methods. 2-{1-[4-(Methylsulfonyl)phenyl]ethylidene}-N-phenylhydrazinecarbothioamide (1) possessed good antioxidant activity with an SC50 value of 15.70 µM which also is higher than standard drug, ascorbic acid. All compounds were evaluated for their antidiabetic properties as α-glycosidase and α-amylase inhibitors. Compound 1 was found to be the most active compound against α-glucosidase and α-amylase with IC50 values of 1.58 µM and 3.24 µM, respectively. The enzyme kinetic studies demonstrated that compound 1 has a competitive mode of binding. Furthermore, molecular docking studies have elucidated the binding mechanism at the molecular level by examining the molecular interactions between compound 1 and these enzymes.