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

Creative Commons License

ÇEVİK U. A., SAĞLIK B. N., OSMANİYE D., LEVENT S., ÇAVUŞOĞLU B. K., KARADUMAN A. B., ...Daha Fazla

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, cilt.35, sa.1, ss.1657-1673, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 35 Sayı: 1
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1080/14756366.2020.1806831
  • Dergi Adı: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, EMBASE, Food Science & Technology Abstracts, MEDLINE, Directory of Open Access Journals
  • Sayfa Sayıları: ss.1657-1673
  • Eskişehir Osmangazi Üniversitesi Adresli: Hayır

Özet

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.