title: Novel taxane derivatives from Taxus wallichiana with high anticancer potency on tumor cells.
abstract: 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.
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, China.|Jiangsu Institute for Food and Drug Control, Nanjing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Center for Drug Safety Evaluation and Research, Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Jiaying
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, China. chyewc@gmail.com.|GuangDong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou, China. chyewc@gmail.com.
authors.forename: Wencai
authors.initials: W
authors.lastname: Ye
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D043823:Taxoids / Q000737:chemistry* / Q000494:pharmacology*; D020946:Taxus / Q000737:chemistry*; D014404:Tubulin / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D010936:Plant Extracts; D043823:Taxoids; D014404:Tubulin; C080625:taxane
keywords: anticancer activity; ethanol extract; taxane derivatives; tubulin polymerization