FLUORESCENT AND BIOTINYLATED ANALOGS 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'-biotinylamido-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 eels. Although addition of microtubules to 1l, 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.