Effects of the hydrophobicity of taxoids on their interaction with tubulin.
Modifications of the hydrophobic character at the 7 and 10 positions of the taxoids greatly modified the effect of these drugs on the tubulin microtubule system. The presence of an alkyl chain at these positions decreased the activity while their corresponding more polar analogues restored the activity of these molecules. It appears that the recognition of taxoids by tubulin depends on the location of the most important hydrophobic area.
Guénard
D
D
Institut de Chimie des Substances Naturelles, CNRS, Gif sur Yvette, France. daniel.guenard@icsn.cnrs-gif.fr
Thoret
S
S
Dubois
J
J
Adeline
M T
MT
Wang
Q
Q
Guéritte
F
F
D000470:Alkaloids / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D004354:Drug Screening Assays, Antitumor; D017239:Paclitaxel / Q000031:analogs & derivatives; D013057:Spectrum Analysis; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D014867:Water / Q000737:chemistry
D000470:Alkaloids; D014404:Tubulin; D014867:Water; D017239:Paclitaxel