Synthesis and topoisomerases inhibitory activity of heteroaromatic chalcones |
| |
Affiliation: | 1. Department of Chemistry, Faculty of Science, Tanta University, Tanta 31527, Egypt;2. Department of Toxic and Narcotic Drug, Forensic Medicine, Mansoura Laboratory, Ministry of Justice, Medico legal Organization, Egypt |
| |
Abstract: | The critical role of nuclear topoisomerase enzymes during cell proliferation process guided topoisomerases to be one of the major targets for anticancer drug development. We have designed and synthesized 22 heteroaromatic ring incorporated chalcone derivatives substituted with epoxide or thioepoxide. Topoisomerase enzyme inhibitory activity and cytotoxic tests were also conducted to evaluate compounds’ pharmacological efficacy. In the topoisomerase I inhibitory test, compound 1 was most active one, 24% of inhibition at 20 μM, among all the compounds but it was lower than camptothecin. Compounds 9, 11, and 13 inhibited the function of topoisomerase II more strongly than etoposide with almost same magnitude (around 90% and 30% inhibition at 100 and 20 μM, respectively) which were higher than those of etoposide (72% and 18% inhibition). In the cytotoxicity test, compound 9 inhibited T47D cancer cell growth with the IC50 value of 6.61 ± 0.21 μM. On the other hand, compound 13 (IC50: 4.32 ± 0.18 μM) effectively suppressed MDA-MB468 cancer cell growth. |
| |
Keywords: | Heteroaromatic chalcones Topoisomerases inhibitors Anticancer activity |
本文献已被 ScienceDirect 等数据库收录! |
|