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

Abstract

AbstractA 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 µM) 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 µM) 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.