Novel ester tethered dihydroartemisinin-3-(oxime/thiosemicarbazide)isatin hybrids as potential anti-breast cancer agents: Synthesis, in vitro cytotoxicity and structure-activity relationship

A series of ester tethered dihydroartemisinin-3-(oxime/thiosemicarbazide)isatin hybrids 7a-p were designed, synthesized, and assessed for their antiproliferative activity against MCF-7, MDA-MB-231, MCF-7/ADR, and MDA-MB-231/ADR breast cancer cell lines. Among them, hybrids 7a,f (IC50: 1.33-3.84 mu M) showed potent activity against triple-negative (MDA-MB-231 and MDA-MB-231/ADR) breast cancer cell lines, and hybrid 7f (IC50: 3.90 and 10.18 mu M) also demonstrated promising activity against estrogen receptor-positive breast cancer cells (MCF-7 and MCF-7/ADR), and the activity was superior to these of artemisinin, dihydroartemisinin, and ADR, revealing their potential to fight against both drug-sensitive and drug-resistant breast cancers. The enriched structure-activity relationships may facilitate further design of more active candidates.

Automated summary

A series of ester tethered dihydroartemisinin-3-(oxime/thiosemicarbazide)isatin hybrids 7a-p were designed, synthesized, and evaluated for their antiproliferative activity against breast cancer cell lines. The hybrids showed potent activity against both drug-sensitive and drug-resistant breast cancers. The structure-activity relationships obtained from this study may aid in the design of more active candidates.