Novel taxane derivatives from Taxus wallichiana with high anticancer potency on tumor cells.
Four novel taxane derivatives, N-debenzoyl-N-methyl-N-heptanoyl-taxol (1), N-debenzoyl-N-me-thyl-N-octanoyl-taxol (2), N-debenzoyl-N-methyl-N-(4-methylhexanoyl)-taxol (3), and N-debenzoyl-N-methyl-N-[(4Z)-1-oxo-4-tenenoyl]-taxol (4), were isolated from the ethanol extract of the whole plant of Taxus wallichiana.var.mairer. These structures were identified on the basis of extensive spectroscopic analysis, and their antitumor activity was evaluated against MCF-7, A549, and 3-AO cancer cell lines by the MTT method. Compound 3, the most promising one, exhibited encouraging effect with IC50 of 77 nm in MCF-7 cells, which was almost matching that of positive control Taxol. In further mechanism study, the tubulin polymerization assay demonstrated that four compounds caused shifts from the soluble tubulin (depolymerized tubulin) to the particulate tubulin fraction (polymerized) which was similar to Taxol. These results revealed novel natural products with paclitaxel-likemicrotu-bule-stabilizing activity owned their major importance in the clinical treatment of cancer.
['Wang|Yong|Y|', 'Wang|Jiaying|J|', 'Wang|Hao|H|', 'Ye|Wencai|W|']
D000072283:A549 Cells D000970:Antineoplastic Agents D001952:Bridged-Ring Compounds D045744:Cell Line, Tumor D049109:Cell Proliferation D006801:Humans D020128:Inhibitory Concentration 50 D061986:MCF-7 Cells D015394:Molecular Structure D010936:Plant Extracts D043823:Taxoids D020946:Taxus D014404:Tubulin
taxane derivatives ethanol extract tubulin polymerization anticancer activity