title: [Design, synthesis and antiproliferative activities of artemisinin derivatives substituted by N-heterocycles].
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.
authors.forename: Zhi-zhong
authors.initials: ZZ
authors.lastname: Zuo
authors.forename: Hang
authors.initials: H
authors.lastname: Zhong
authors.forename: Ting
authors.initials: T
authors.lastname: Cai
authors.forename: Yu
authors.initials: Y
authors.lastname: Bao
authors.forename: Zhi-qiang
authors.initials: ZQ
authors.lastname: Liu
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.forename: Lin-xiang
authors.initials: LX
authors.lastname: Zhao
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry*; D037621:Artemisinins / Q000138:chemical synthesis / Q000737:chemistry*; D001943:Breast Neoplasms / Q000473:pathology; D049109:Cell Proliferation; D004317:Doxorubicin; D015195:Drug Design; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D037621:Artemisinins; C039060:artenimol; D004317:Doxorubicin