Synthesis and tubulin-binding properties of non-symmetrical click C5-curcuminoids

Bioorg Med Chem. 2013 Sep 1;21(17):5510-7. doi: 10.1016/j.bmc.2013.05.053. Epub 2013 Jun 13.

Abstract

A click-type entry into shortened curcuminoids of the diarylpentanoid type has been developed. The reaction is ideally suited to generate non-symmetrical analogues of curcumin, a class of natural products difficult to access but of growing biomedical relevance and special mechanistic interest to investigate the unique binding mode of curcumin to tubulin. Investigation of a series of click diarylpentane curcuminoids and their pyrazole adducts in various cellular tubulin functional assays validated this class of compounds as a novel type of anti-mitotic agents, evidencing structure-activity relationships, and identifying the pyrazole adduct 4k as a promising lead.

Keywords: Antimitotic agents; Click chemistry; Curcumin; Curcuminoids; Tubulin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Curcumin / analogs & derivatives*
  • Curcumin / chemical synthesis
  • Curcumin / toxicity
  • Humans
  • Pyrazoles / chemistry
  • Structure-Activity Relationship
  • Tubulin / chemistry*
  • Tubulin / metabolism
  • Tubulin Modulators / chemical synthesis*
  • Tubulin Modulators / chemistry
  • Tubulin Modulators / toxicity

Substances

  • Pyrazoles
  • Tubulin
  • Tubulin Modulators
  • pyrazole
  • Curcumin