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Novel taxane derivatives from Taxus wallichiana with high anticancer potency on tumor cells
Author(s) -
Wang Yong,
Wang Jiaying,
Wang Hao,
Ye Wencai
Publication year - 2016
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12782
Subject(s) - taxane , paclitaxel , tubulin , taxus , chemistry , potency , mtt assay , microtubule , stereochemistry , microtubule polymerization , in vitro , pharmacology , cancer , biochemistry , biology , botany , genetics , breast cancer , microbiology and biotechnology
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 IC 50 of 77 n m 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.