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), H-1-NMR and C-13-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 mu M which also is higher than standard drug, ascorbic acid. All compounds were evaluated for their antidiabetic properties as alpha-glycosidase and alpha-amylase inhibitors. Compound 1 was found to be the most active compound against alpha-glucosidase and alpha-amylase with IC50 values of 1.58 mu M and 3.24 mu M, 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.