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

ÇELİK İ., ACAR ÇEVİK U., Küçükoğlu K., NADAROĞLU H., BOSTANCI H. E., Işık A., ...Daha Fazla

Chemical Biology and Drug Design, cilt.103, sa.1, 2024 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 103 Sayı: 1
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1111/cbdd.14351
  • Dergi Adı: Chemical Biology and Drug Design
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: 1,3,4-triazole, antioxidant, benzimidazole, carbonic anhydrase, molecular docking
  • Sivas Cumhuriyet Üniversitesi Adresli: Evet

Özet

In 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 1H-NMR, 13C-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 μM–3.122 μM. Among all these compounds, compound 5e, with an IC50 value of 1.288 μM is the most active against carbonic hCA I. Compound 5h with an IC50 value of 1.532 μM 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.