Synthesis and biological evaluation of paclitaxel-thiocolchicine hybrids

Chem Biodivers. 2004 Feb;1(2):327-45. doi: 10.1002/cbdv.200490029.

Abstract

The bifunctional taxoid-colchicinoid hybrids 6-8 were synthesized and evaluated in assays of cytotoxicity and tubulin assembly/disassembly. All compounds showed a high degree of cytotoxicity, but, while 6 and 7 behaved as bifunctional tubulin binders not unlike an equimolecular mixture of taxol and thiocolchicine, 8 was surprisingly devoid of tubulin activity, acting on a distinct and yet to identify molecular target.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols* / chemical synthesis
  • Antineoplastic Combined Chemotherapy Protocols* / pharmacology
  • Cattle
  • Cell Line, Tumor
  • Colchicine / analogs & derivatives*
  • Colchicine / chemical synthesis
  • Colchicine / pharmacology
  • Drug Screening Assays, Antitumor / methods
  • Humans
  • Microtubules / drug effects
  • Microtubules / physiology
  • Paclitaxel / chemical synthesis*
  • Paclitaxel / pharmacology*

Substances

  • thiocholchicine
  • Paclitaxel
  • Colchicine