Fluorescent and biotinylated analogues of docetaxel: synthesis and biological evaluation.
Six novel docetaxel analogues that possess a N-(7-nitrobenz-2-oxa-1,3-diazo-4-yl)amido-6-caproyl chain in position 7 or 3' (11 and 16a), a N-(7-nitrobenz-2-oxa-1,3-diazo-4-yl)amido-3-propanoyl group at 3' (16b) and a 5'-biotinyl amido-6-caproyl chain in position 7, 10 or 3', respectively, have been synthesized. These compounds exhibit activity against microtubule disassembly similar to that of docetaxel but show discrepant activities on living cells. Although addition of microtubules to 11, 16a and b enhance their fluorescence, no shift of the emission maxima was observed. The fluorescent docetaxel derivatives show a specific labeling of microtubules in living cells, demonstrating that the microtubule cytoskeleton constitutes their main subcellular localization.
Dubois
J
J
Institut de Chimie des Substances Naturelles, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France.
Le Goff
M T
MT
Guéritte-Voegelein
F
F
Guénard
D
D
Tollon
Y
Y
Wright
M
M
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000737:chemistry; D001360:Avidin / Q000737:chemistry; D001710:Biotin / Q000737:chemistry; D001923:Brain Chemistry; D002417:Cattle; D002478:Cells, Cultured; D000077143:Docetaxel; D005456:Fluorescent Dyes / Q000138:chemical synthesis; D007614:Macropodidae; D009682:Magnetic Resonance Spectroscopy; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D043823:Taxoids; D014404:Tubulin / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D005456:Fluorescent Dyes; D043823:Taxoids; D014404:Tubulin; D001360:Avidin; D000077143:Docetaxel; D001710:Biotin; D017239:Paclitaxel