Design, synthesis, and molecular docking studies of benzimidazole-1,3,4-triazole hybrids as carbonic anhydrase I and II inhibitors

ÇELİK İ., Cevik U. A., Kucukoglu K., NADAROĞLU H., BOSTANCI H. E., Isik A., ...More

CHEMICAL BIOLOGY & DRUG DESIGN, vol.103, no.1, 2024 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 103 Issue: 1
  • Publication Date: 2024
  • Doi Number: 10.1111/cbdd.14351
  • Journal Name: CHEMICAL BIOLOGY & DRUG DESIGN
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Keywords: 1,3,4-triazole, antioxidant, benzimidazole, carbonic anhydrase, molecular docking
  • Anadolu University Affiliated: Yes

Abstract

n this study, with an aim to develop novel heterocyclic hybrids as potent enzyme inhibitors, we synthesized a series of 10 novel 2-(4-(4-ethyl-5-(2-(substitutedphenyl)-2-oxo-ethylthio)-4H-1,2,4-triazol-3-yl)-phenyl)-5,6-dimethyl-1H-benzimidazole (5a-5j) derivatives and characterized by H-1-NMR, C-13-NMR, and HRMS. These compounds were evaluated for their inhibitory activity against hCA I and hCA II. All the compounds exhibited good hCA I and hCA II inhibitory activities with IC50 values in range of 1.288 mu M-3.122 mu M. Among all these compounds, compound 5e, with an IC50 value of 1.288 mu M is the most active against carbonic hCA I. Compound 5h with an IC50 value of 1.532 mu M is the most active against carbonic hCA-II. Compounds 5a-5j were also evaluated for their cytotoxic effects on the L929 mouse fibroblast (normal) cell line. The compounds were also analyzed for their antioxidant capacity by TAS, FRAP, and DPPH activity. Enzyme inhibition kinetics showed all compounds 5a-5j to inhibit the enzyme by non-competitive. The most active compound 5e for hCA I and compound 5h for hCA-II were subjected to molecular docking, which revealed their binding interactions with the enzyme's active site, confirming the experimental findings.