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

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

Keywords:

• Benzenesulfonamide
• 1,2,3-triazole
• carbonic anhydrase
• ADMET
• molecular docking

Disclosure statement

The authors declare no conflict of interest.

Scheme 1. Synthesis steps followed for the synthesis of compounds 5a–d

Scheme 2. Synthesis steps followed for the synthesis of compounds 9a–h

Additional information

Funding

We are grateful to Kahramanmaras Sutcu Imam University Research Unit (Project number: 2019/1-17D) for the financial support. Furthermore, we would like to thank the Higher Education Council Research Board (YÖK 100/2000 PhD. Scholarship Priority Areas Program field: 02.01.02 ‘Molecular Pharmacology and Pharmaceutical Research’) for granting the Scholarship (to Seyit Ali Güngör).