Microtubule interactions with chemically diverse stabilizing agents: Thermodynamics of binding to the paclitaxel site predicts cytotoxicity Academic Article uri icon

Overview

MeSH Major

  • Antineoplastic Agents
  • Microtubules
  • Paclitaxel

abstract

  • The interactions of microtubules with most compounds described as stabilizing agents have been studied. Several of them (lonafarnib, dicumarol, lutein, and jatrophane polyesters) did not show any stabilizing effect on microtubules. Taccalonolides A and E show paclitaxel-like effects in cells, but they were not able to modulate in vitro tubulin assembly or to bind microtubules, which suggests that other factors are involved in their cellular effects. The binding constants of epothilones, eleutherobin, discodermolide, sarcodictyins, 3,17beta-diacetoxy-2-ethoxy-6-oxo-B-homo-estra-1,3,5(10)-triene, and dictyostatin to the paclitaxel site; the critical concentrations of ligand-induced assembly; and their cytotoxicity in carcinoma cells have been measured, and correlations between these parameters have been determined. The inhibition of cell proliferation correlates better with the binding enthalpy change than with the binding constants, suggesting that large, favorable enthalpic contribution to the binding is desired to design paclitaxel site drugs with higher cytotoxicity.

publication date

  • December 2005

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1016/j.chembiol.2005.09.010

PubMed ID

  • 16356844

Additional Document Info

start page

  • 1269

end page

  • 79

volume

  • 12

number

  • 12