Preparation and evaluation of new brominated paclitaxel analogues

J Asian Nat Prod Res. 2005 Jun;7(3):231-6. doi: 10.1080/10286020410001690118.

Abstract

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.

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Bromine
  • Cell Line, Tumor
  • Humans
  • Paclitaxel / analogs & derivatives*
  • Paclitaxel / chemical synthesis
  • Paclitaxel / pharmacology
  • Stereoisomerism

Substances

  • Antineoplastic Agents
  • Paclitaxel
  • Bromine