Preparation and evaluation of new brominated paclitaxel analogues.
Two diastereomers of 2'',3''-dibromo-7-epi-10-deacetylcephalomannine, 4 and 5, have been synthesized, purified and identified for evaluation as antitumour drugs. The cytotoxicity of the two diastereomers, assessed in cell culture against MCF-7 breast cancer, A549 lung cancer and A2780 ovarian cancer, was slightly stronger than that of paclitaxel. The cytotoxicity of 5 outweighs that of 4. In the light of the difference in cytotoxicity between the two diastereomers, we can assume that the differing configurations of C-2'' and C-3'' of the two diastereomers may result in different bioactive conformations in solution and, consequently, different biologically relevant conformations for binding to tubulin/microtubules -- a matter we are studying further.
Jiang
Yi
Y
Department of Environmental Science and Engineering, Fudan University, Shanghai 200433, China.
Lin
Hai-Xia
HX
Li
Ming
M
Wu
Bei-Li
BL
Chen
Jian-Min
JM
D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D001966:Bromine; D045744:Cell Line, Tumor; D006801:Humans; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D013237:Stereoisomerism
D000970:Antineoplastic Agents; D017239:Paclitaxel; D001966:Bromine