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.

摘要

在这项研究中，合成了一些苯并咪唑-恶二唑衍生物，并测试了它们对包括HeLa，MCF7，A549，HepG2和C6在内的五种癌细胞系的体外抗癌活性。通过IR，¹ H-NMR，¹³ C-NMR，2 D-NMR和HRMS光谱法阐明了它们的结构。在所有筛选的化合物中；图5a，5b，5d，5e，5k，5l，5n和5o对各种测试的癌细胞系表现出有效的选择性细胞毒性活性。特别是化合物5l和5n与Heechst 33342和阿霉素相比，其对HeLa细胞系的增殖活性最高，IC _50分别为0.224±0.011 µM和0.205±0.010 µM。此外，根据它们对拓扑异构酶I的抑制能力评估了这些有效的铅细胞毒剂，并且确定了所选化合物抑制了拓扑异构酶I。进行了对接研究，并确定了DNA-拓扑I酶复合物中可能的相互作用。