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

TOK F., KÜÇÜKAL B., BALTAŞ N., TATAR YILMAZ G., KAYMAKÇIOĞLU B.

PHOSPHORUS SULFUR AND SILICON AND THE RELATED ELEMENTS, vol.197, no.12, pp.1284-1294, 2022 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 197 Issue: 12
  • Publication Date: 2022
  • Doi Number: 10.1080/10426507.2022.2099857
  • Journal Name: PHOSPHORUS SULFUR AND SILICON AND THE RELATED ELEMENTS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chemical Abstracts Core
  • Page Numbers: pp.1284-1294
  • Keywords: Thiosemicarbazones, alpha-glucosidase, alpha-amylase, antioxidant, molecular docking, ALPHA-AMYLASE, GLUCOSIDASE INHIBITORS, DISCOVERY, OXIDASE
  • Karadeniz Technical University Affiliated: Yes

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.