Design, synthesis and antiproliferative activities of artemisinin derivatives substituted by N-heterocycles.
- Author:
Zhi-zhong ZUO
;
Hang ZHONG
;
Ting CAI
;
Yu BAO
;
Zhi-qiang LIU
;
Dan LIU
;
Lin-xiang ZHAO
- Publication Type:Journal Article
- MeSH:
Antineoplastic Agents;
chemical synthesis;
chemistry;
Artemisinins;
chemical synthesis;
chemistry;
Breast Neoplasms;
pathology;
Cell Proliferation;
Doxorubicin;
Drug Design;
HL-60 Cells;
drug effects;
Humans;
MCF-7 Cells;
drug effects
- From:
Acta Pharmaceutica Sinica
2015;50(7):868-874
- CountryChina
- Language:Chinese
-
Abstract:
Increasing attention has been focused on the antitumor activity of artemisinin derivatives in recent years, for artemisinin had been reported to have cytotoxic effects against HL-60, P388 and MCF-7 tumor cells. We report here the synthesis and evaluation for antitumor activity of a series of artemisinin-ether derivatives bearing tetrahydropyrrole, morpholine, piperidine, substituted piperidines and azoles with various linkers. Sixteen 10-O-substituted dihydroartemisinin derivatives were designed and synthesized, all of which have never been reported in literatures and whose antiproliferative effects on human breast cancer MCF-7, MCF-7/Adr and HL-60 cells were determined by MTT assay or direct cell counting. Each of these artemisinin derivatives possessed better effects than dihydroartemisinin evidently against HL-60 and MCF-7 cells growth, while less potent than doxorubicin. All target compounds exhibited significantly improved potency compared to DHA and doxorubicin on the doxorubicin-resistant MCF-7/Adr cells, so did they in their sensitive counterparts MCF-7 cells. Among them, compounds GF02, GH04 and ZH04 showed strong activity against these three cell lines growth. Further research is undergoing.
