title: Isolation and cytotoxicity evaluation of taxanes from the barks of Taxus wallichiana var. mairei.
abstract: Fifteen taxanes (1-15) including a new taxane glucoside, 7β,9α,10β-triacetoxy-13α-hydroxy-5α-O-(β-d-glucopyranosyl)taxa-4(20),11-diene (1), were isolated from the barks of Taxus wallichiana var. mairei. Compounds 1-15 representing three sub-types of 6/8/6-taxane were evaluated in vitro for anti-proliferative activity against a panel of parental and drug-resistant cancer cells. Potent compounds were found while several exhibited selective cytotoxicity. Especially, 3, 8, and 10 showed selective inhibition to breast carcinoma cell line MCF-7, while 13 selectively inhibited taxol resistant human ovarian carcinoma cell line A2780/TAX (IC50=0.19μM), being more potent than the clinical drugs taxol (IC50=4.4μM) and docetaxol (IC50=0.42μM), and less cytotoxic to mouse embryonic fibroblast cell line NIH-3T3, a cell line close to normal cell line. The possible P-glycoprotein evasion mechanism of 13 against A2780/TAX and the preliminary structure-activity relationships (SARs) of this group of compounds were also discussed.
authors: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, People's Republic of China.
authors: Zhang-Hua
authors: ZH
authors: Sun
authors: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, People's Republic of China.
authors: Yu
authors: Y
authors: Chen
authors: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, People's Republic of China.
authors: Yan-Qiong
authors: YQ
authors: Guo
authors: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, People's Republic of China.
authors: Jie
authors: J
authors: Qiu
authors: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, People's Republic of China.
authors: Cui-Ge
authors: CG
authors: Zhu
authors: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, People's Republic of China.
authors: Jing
authors: J
authors: Jin
authors: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, People's Republic of China.
authors: Gui-Hua
authors: GH
authors: Tang
authors: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, People's Republic of China. Electronic address: phsbxzh@mail.sysu.edu.cn.
authors: Xian-Zhang
authors: XZ
authors: Bu
authors: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, People's Republic of China. Electronic address: yinsh2@mail.sysu.edu.cn.
authors: Sheng
authors: S
authors: Yin
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008968:Molecular Conformation; D041681:NIH 3T3 Cells; D017239:Paclitaxel / Q000494:pharmacology; D024301:Plant Bark / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D043823:Taxoids / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D020946:Taxus / Q000737:chemistry* / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D043823:Taxoids; C000603769:taxacin; D017239:Paclitaxel
keywords: Cytotoxicity; Drug resistant; Structure–activity relationships; Taxanes; Taxus wallichiana var. mairei