Synthesis, characterization and docking studies of benzenesulfonamide derivatives containing 1,2,3-triazole as potential inhibitor of carbonic anhydrase I-II enzymes


Gungor S. A., KÖSE M., TÜMER M., TÜRKEŞ C., BEYDEMİR Ş.

JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, vol.41, no.20, pp.10919-10929, 2023 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 41 Issue: 20
  • Publication Date: 2023
  • Doi Number: 10.1080/07391102.2022.2159531
  • Journal Name: JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE
  • Page Numbers: pp.10919-10929
  • Keywords: 1,2,3-triazole, ADMET, Benzenesulfonamide, carbonic anhydrase, molecular docking
  • Anadolu University Affiliated: Yes

Abstract

Carbonic Anhydrases (CAs) are an important family of metalloenzymes that contain zinc (Zn2+) ions in their active site and catalyze the conversion of carbon dioxide to bicarbonate and proton and found in all living organisms. Sulfonamides are well-known inhibitors of CAs isoenzymes. In this study, a series of benzenesulfonamide derivatives (9a-h) containing 1,2,3-triazole-moiety were designed, synthesized and their structures were characterized by spectroscopic methods. In addition, molecular structures of compounds 5a, 5 b, 9e and 9f were elucidated by X-ray diffraction technique. To investigate drug similarity of 9a-h compounds, Lipinski's five rules (ADMET: absorption, distribution, metabolism, excretion and toxicity) were carried out by in silico studies. According to results, the compounds showed drug-like properties. Docking studies were applied to determine the scores, interactions and binding modes of compounds 9a-h against hCA I and hCA II enzymes. Compound 9c (-5.13 kcal/mol docking score) against hCA I enzyme and 9 h (-5.32 kcal/mol docking score) against hCA II enzyme showed potent inhibitory properties. The binding interactions of the compounds with the carbonic anhydrases were examined by docking studies.Communicated by Ramaswamy H. Sarma