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

Fifteen taxanes (1-15) including a new taxane glucoside, 7 beta, 9 alpha, 10 beta-triacetoxy-13 alpha-hydroxy-5 alpha-O-(beta-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 = 0.19 mu M), being more potent than the clinical drugs taxol (IC50 = 4.4 mu M) and docetaxol (IC50 = 0.42 mu M), 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. (C) 2015 Elsevier Ltd. All rights reserved.