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

ACAR ÇEVİK U., SAĞLIK B. N., OSMANİYE D., LEVENT S., ÇAVUŞOĞLU B. K., KARADUMAN A. B., ...More

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, vol.35, no.1, pp.1657-1673, 2020 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 35 Issue: 1
  • Publication Date: 2020
  • Doi Number: 10.1080/14756366.2020.1806831
  • Journal Name: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, EMBASE, Food Science & Technology Abstracts, MEDLINE, Directory of Open Access Journals, Index Chemicus (IC)
  • Page Numbers: pp.1657-1673
  • Keywords: Benzimidazole, 1, 3, 4-oxadiazole, anticancer, DNA Topo I, Hoechst 33342, BIOLOGICAL EVALUATION, BENZIMIDAZOLES, INHIBITORS, DISCOVERY, NUCLEUS, DESIGN
  • Bilecik Şeyh Edebali University Affiliated: No

Abstract

In this study, some benzimidazole-oxadiazole derivatives were synthesised and tested for theirin vitroanticancer activities on five cancer cell lines, including HeLa, MCF7, A549, HepG2 and C6. Their structures were elucidated by IR,H-1-NMR,C-13-NMR, 2 D-NMR and HRMS spectroscopic methods. Among all screened compounds;5a,5b,5d,5e,5k,5l,5nand5oexhibited potent selective cytotoxic activities against various tested cancer cell lines. Especially, compounds5land5nexhibited the most antiproliferative activity than Hoechst 33342 and doxorubicin against HeLa cell line, with IC(50)of 0.224 +/- 0.011 mu M and 0.205 +/- 0.010 mu M, 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.