Replacement of the double bond of antitubulin chalcones with triazoles and tetrazoles: Synthesis and biological evaluation

Bioorg Med Chem Lett. 2011 Jan 15;21(2):764-8. doi: 10.1016/j.bmcl.2010.11.113. Epub 2010 Nov 28.

Abstract

In the chalcone scaffold, it is thought that the double bond is an important structural linker but it is likely not essential for the interaction with tubulin. Yet, it may be a potential site of metabolic degradation and interaction with biological nucleophiles. In this letter, we have replaced this olefinic portion of chalcones with two metabolically stable and chemically inert heterocyclic rings, namely triazole or tetrazole. Yet, our biologic data suggest that, unlike in other antitubulinic structures, the olephinic ring might not be merely a structural linker.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Chalcones / chemical synthesis
  • Chalcones / chemistry*
  • Chalcones / pharmacology*
  • Humans
  • Models, Molecular
  • Neuroblastoma / drug therapy
  • Tetrazoles / chemical synthesis
  • Tetrazoles / chemistry*
  • Tetrazoles / pharmacology*
  • Triazoles / chemical synthesis
  • Triazoles / chemistry*
  • Triazoles / pharmacology*
  • Tubulin / metabolism
  • Tubulin Modulators / chemical synthesis
  • Tubulin Modulators / chemistry*
  • Tubulin Modulators / pharmacology*

Substances

  • Antineoplastic Agents
  • Chalcones
  • Tetrazoles
  • Triazoles
  • Tubulin
  • Tubulin Modulators