Synthesis, anticancer evaluation and molecular docking studies of new benzimidazole- 1,3,4-oxadiazole derivatives as human topoisomerase types I poison

Abstract

In this study, some benzimidazole-oxadiazole derivatives were synthesised and tested for their in vitro anticancer activities on five cancer cell lines, including HeLa, MCF7, A549, HepG2 and C6. Their structures were elucidated by IR, ¹H-NMR, ¹³C-NMR, 2 D-NMR and HRMS spectroscopic methods. Among all screened compounds; 5a, 5b, 5d, 5e, 5k, 5l, 5n and 5o exhibited potent selective cytotoxic activities against various tested cancer cell lines. Especially, compounds 5l and 5n exhibited the most antiproliferative activity than Hoechst 33342 and doxorubicin against HeLa cell line, with IC₅₀ of 0.224 ± 0.011 µM and 0.205 ± 0.010 µM, respectively. Furthermore, these potent lead cytotoxic agents were evaluated in terms of their inhibition potency against Topoisomerase I and it was determined that selected compounds inhibited the Topoisomerase I. Docking studies were performed and probable interactions in the DNA-Topo I enzyme complex was determined.

Keywords:

• Benzimidazole
• 1,3,4-oxadiazole
• anticancer
• DNA Topo I
• Hoechst 33342

Disclosure statement

The authors declare no conflicts of interest.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This study was financially supported by Anadolu University Scientific Projects Fund, Project No: 2005S036 and 1706S381.