2. Academic Validation
  3. Isolation and cytotoxicity evaluation of taxanes from the barks of Taxus wallichiana var. mairei

Isolation and cytotoxicity evaluation of taxanes from the barks of Taxus wallichiana var. mairei

  • Bioorg Med Chem Lett. 2015 Mar 15;25(6):1240-3. doi: 10.1016/j.bmcl.2015.01.056.
Zhang-Hua Sun 1,  Yu Chen 1,  Yan-Qiong Guo 1,  Jie Qiu 2,  Cui-Ge Zhu 1,  Jing Jin 1,  Gui-Hua Tang 1,  Xian-Zhang Bu 3,  Sheng Yin 4
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, People's Republic of China.
  • 2 School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, People's Republic of China.
  • 3 School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, People's Republic of China. Electronic address: phsbxzh@mail.sysu.edu.cn.
  • 4 School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, People's Republic of China. Electronic address: yinsh2@mail.sysu.edu.cn.
PMID: 25682561 DOI: 10.1016/j.bmcl.2015.01.056
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.

Keywords

Cytotoxicity; Drug resistant; Structure–activity relationships; Taxanes; Taxus wallichiana var. mairei.

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