Design, synthesis and antiproliferative activities of artemisinin derivatives substituted by N-heterocycles / 药学学报
Acta Pharmaceutica Sinica
; (12): 868-874, 2015.
Article
in Zh
| WPRIM
| ID: wpr-257054
Responsible library:
WPRO
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.
Full text:
1
Index:
WPRIM
Main subject:
Pathology
/
Breast Neoplasms
/
Drug Design
/
Doxorubicin
/
Chemistry
/
HL-60 Cells
/
Artemisinins
/
Cell Proliferation
/
MCF-7 Cells
/
Antineoplastic Agents
Limits:
Humans
Language:
Zh
Journal:
Acta Pharmaceutica Sinica
Year:
2015
Type:
Article