Relationship between the structures of taxane derivatives and their microtubule polymerization activity.
Paclitaxel (Taxol), one of the most potent anticancer drugs, is a microtubule-stabilizing compound that inhibits microtubule depolymerization within the cell. The structure of paclitaxel is composed of two key elements, a taxane ring and an N-benzoylphenylisoserine side chain at C-13. A number of natural and artificial compounds with taxane skeletons have been isolated, but almost none of their bioactivities have been evaluated. In this study, we focused on compounds having a taxane skeleton structure and examined their effects on tubulin dynamics. Although none of these compounds had an N-benzoylphenylisoserine side chain, three were found to promote tubulin assembly. On the other hand, one compound inhibited tubluin assembly in a way similar to nocodazole. These compounds exhibited novel structure-activity relationships of taxane compounds.
Molecular Enzymology, Department of Molecular Cell Science, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
Masafumi
M
Hidaka
Tomoe
T
Koga
Hiromasa
H
Kiyota
Tohru
T
Horiguchi
Qing-Wen
QW
Shi
Keiko
K
Hirose
Takafumi
T
Uchida
D000818:Animals; D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism; D015394:Molecular Structure; D015739:Nocodazole; D017239:Paclitaxel; D058105:Polymerization; D013329:Structure-Activity Relationship; D043823:Taxoids / Q000737:chemistry* / Q000494:pharmacology*; D014404:Tubulin
D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D043823:Taxoids; D014404:Tubulin; C080625:taxane; D017239:Paclitaxel; D015739:Nocodazole