Design, synthesis, molecular docking and molecular dynamic studies of novel benzimidazole-thiazole derivatives as potent and selective COX-2 inhibitors

IRMAK N. E., SAĞLIK ÖZKAN B. N., ÇELİK İ., ŞEN H. T., ÖZKAY Y., Ayhan-Kilcigil G.

NEW JOURNAL OF CHEMISTRY, vol.47, no.47, pp.21620-21632, 2023 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 47 Issue: 47
  • Publication Date: 2023
  • Doi Number: 10.1039/d3nj04438f
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Biotechnology Research Abstracts, Chemical Abstracts Core, Chimica, Compendex, DIALNET
  • Page Numbers: pp.21620-21632
  • Anadolu University Affiliated: Yes


A novel class of benzimidazole-thiazole products have been designed as potential inhibitors of cyclooxygenase, and the synthesized compound structures were verified using instrumental analysis techniques. The in vitro inhibitory effect on COX-1 was dose-dependent, with a significant reduction in effectiveness at lower concentrations. Among the compounds (7b) (IC50 0.297 mu M) (7c) (IC50 0.311 mu M) (8b) (IC50 0.279 mu M) and (8c) (IC50 0.215 mu M), which are the most active compounds, IC50 values were close to celecoxib (IC50 0.132 mu M) against COX-2. Molecular docking studies were carried out on compounds against COX-2 using Glide XP. The compounds 7b, 7c, 8b, and 8c demonstrated significant docking scores of -8.927 kcal mol-1, -8.578 kcal mol-1, -8.485 kcal mol-1, and -8.899 kcal mol-1, respectively, which suggest a promising interaction with the COX-2 enzyme. Moreover, molecular dynamics simulations of 100 ns duration were performed with COX-2 and active compound complexes using Gromacs. The dynamic simulation results support the findings from the molecular docking studies and suggest that compounds 7b, 7c, 8b, and 8c may have the potential to act as potent and selective COX-2 inhibitors. New benzimidazole-thiazole compounds were synthesized to selectively inhibit COX-2.