Dubois J, Le Goff M T, Guéritte-Voegelein F, Guénard D, Tollon Y, Wright M
Institut de Chimie des Substances Naturelles, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France.
Bioorg Med Chem. 1995 Oct;3(10):1357-68. doi: 10.1016/0968-0896(95)00115-w.
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.
已合成了六种新型多西他赛类似物，它们在7位或3'位（11和16a）具有N-（7-硝基苯并-2-恶唑-1,3-二氮杂-4-基）氨基-6-己酰基链，在3'位具有N-（7-硝基苯并-2-恶唑-1,3-二氮杂-4-基）氨基-3-丙酰基（16b），以及分别在7位、10位或3'位具有5'-生物素基氨基-6-己酰基链。这些化合物表现出与多西他赛类似的抗微管解聚活性，但对活细胞的活性存在差异。尽管向11、16a和b中添加微管会增强它们的荧光，但未观察到发射最大值的位移。荧光多西他赛衍生物在活细胞中显示出对微管的特异性标记，表明微管细胞骨架构成了它们主要的亚细胞定位。
