Artemisinin-isatin hybrids with potential antiproliferative activity against breast cancer

Three series of artemisinin-isatin hybrids 8a-i, 10a-c and 11a-e were designed, synthesized and evaluated for their antiproliferative activity against breast cancer cells (MCF-7, MDA-MB-231 and doxorubicin-resistant MCF-7 (MCF-7/DOX)), as well as the cytotoxicity towards normal MCF-10A breast cells. The preliminary results showed that a significant part of the synthesized hybrids (IC50: 20.7-99.9 mu M) were active against both drug-sensitive and doxorubicin-resistant breast cancer cell lines. The structure-activity relationship illustrated that the linker between artemisinin and isatin moieties as well as the substituents on C-3 and C-5 position of isatin motif had great influence on the activity. In particular, hybrids 11c,d were found to be most active against all tested breast cancer cell lines, and their activity was not inferior to that of doxorubicin. Therefore, hybrids 11c,d could serve as useful templates for the development of novel anti-breast cancer agents. (C) 2021 The Author(s). Published by Elsevier B.V. on behalf of King Saud University.

Automated summary

This study designed and synthesized a series of artemisinin-isatin hybrids and evaluated their antiproliferative activity against breast cancer cells. The preliminary results showed that some of the hybrids exhibited activity against both drug-sensitive and doxorubicin-resistant breast cancer cell lines. Structure-activity relationship analysis revealed the significant influence of linker and substituents on the activity. Certain hybrids displayed the most active anti-cancer activity, comparable to doxorubicin. Therefore, these hybrids could serve as important templates for developing novel anti-breast cancer agents.