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, 1 H-NMR, 13 C-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 IC 50 of 0.224 ± 0.011 mM and 0.205 ± 0.010 mM, 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.

Design, Synthesis, and Molecular Modeling Studies of a Novel Benzimidazole as an Aromatase Inhibitor

“…After the additions, the reaction mixture was stirred for 1 h at room temperature. 16 The precipitated product was filtered, washed, and dried.…”

“…The mixture was cooled and then poured into ice water, filtered, rinsed with water, dried, and recrystallized from EtOH. 16 …”

“…The mixture was refluxed for 8 h. The solution was cooled and acidified to pH 4–5 using concentrated hydrochloric acid solution after the reaction was completed to obtain the target compound. 16 …”

“…In acetone were dissolved compounds 4a – c (0.001 mol), potassium carbonate (0.001 mol, 0.138 g), and 2-chloro-1-(4-substituted epiperazin-1-yl)ethane-1-one (0.0015 mol) and refluxed for 6 h. The solvent was evaporated after TLC control, the residue was washed with water, dried, and then recrystallized from ethanol to produce final compounds 5a – i . 16 …”

“…In our previous studies, we synthesized a series of benzimidazole-oxadiazole derivatives which showed satisfactory anticancer activity with good IC 50 values against various cell lines. 16 , 17 As part of a continuing effort to find out and screen more active benzimidazole-oxadiazole derivatives, in the present study, a series of novel 4-phenyl- and 4-piperazinyl-substituted 2-{[5-(2-phenyl-1 H -benzo[ d ]imidazol-6-yl)-1,3,4-oxadiazol-2-yl]thio}-1-piperazin-1-ylethan-1-one derivatives were synthesized which were later confirmed by 1 H NMR, 13 C NMR, and mass spectral techniques. Then, their cytotoxic activities against various cancer cell lines including A549 (human lung adenocarcinoma epithelial cell line), HepG2 (human colon cancer cell line), MCF-7 (breast adenocarcinoma), C6 (breast adenocarcinoma), and HeLa (ovarian cancer cell line) were evaluated.…”