The Mechanism of the Interactions of Pironetin Analog/Combretastatin A-4 Hybrids with Tubulin

Arch Pharm (Weinheim). 2015 Aug;348(8):541-7. doi: 10.1002/ardp.201500106. Epub 2015 Jun 17.

Abstract

We here report an investigation of the interactions with tubulin of two types of molecules of a hybrid structural type consisting in a combretastatin A-4 moiety and a simplified pironetin fragment. The cytotoxicities of the molecules on two reference tumoral cell lines were measured. In addition, the effects of the compounds on the cell cycle and on microtubule assembly were observed. The dynamics of microtubule polymerization was investigated by means of immunofluorescence assays. It was thus established that at least some of the compounds under study exert their cytotoxic action by means of interaction with tubulin.

Keywords: Combretastatin A-4 derivatives; Cytotoxic compounds; Hybrid molecules; Microtubules; Pironetin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cell Cycle / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Design*
  • HT29 Cells
  • Humans
  • Inhibitory Concentration 50
  • Microtubules / drug effects
  • Microtubules / metabolism
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism*
  • Peptide Fragments / pharmacology
  • Polymerization
  • Protein Binding
  • Protein Conformation
  • Pyrones / chemistry
  • Pyrones / metabolism*
  • Pyrones / pharmacology
  • Stilbenes / chemistry
  • Stilbenes / metabolism*
  • Stilbenes / pharmacology
  • Structure-Activity Relationship
  • Tubulin / chemistry
  • Tubulin / drug effects
  • Tubulin / metabolism*
  • Tubulin Modulators / chemistry
  • Tubulin Modulators / metabolism*
  • Tubulin Modulators / pharmacology

Substances

  • Peptide Fragments
  • Pyrones
  • Stilbenes
  • Tubulin
  • Tubulin Modulators
  • pironetin
  • fosbretabulin