Synthesis and biological evaluation of [6]-gingerol analogues as transient receptor potential channel TRPV1 and TRPA1 modulators

Bioorg Med Chem Lett. 2012 Feb 15;22(4):1674-7. doi: 10.1016/j.bmcl.2011.12.113. Epub 2011 Dec 31.

Abstract

In order to explore the structural determinants for the TRPV1 and TRPA1 agonist properties of gingerols, a series of nineteen analogues (1b-5) of racemic [6]-gingerol (1a) was synthesized and tested on TRPV1 and TRPA1 channels. The exploration of the structure-activity relationships, by modulating the three pharmacophoric regions of [6]-gingerol, led to the identification of some selective TRPV1 agonists/desensitizers of TRPV1 channels (3a, 3f, and 4) and of some full TRPA1 antagonists (2c, 2d, 3b, and 3d).

MeSH terms

  • Calcium Channels
  • Catechols / chemical synthesis*
  • Catechols / chemistry
  • Catechols / pharmacology
  • Fatty Alcohols / chemical synthesis*
  • Fatty Alcohols / chemistry
  • Fatty Alcohols / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Molecular Structure
  • Nerve Tissue Proteins / agonists*
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Protein Binding / drug effects
  • Stereoisomerism
  • Structure-Activity Relationship
  • TRPA1 Cation Channel
  • TRPV Cation Channels / agonists*
  • TRPV Cation Channels / antagonists & inhibitors
  • Transient Receptor Potential Channels / agonists*
  • Transient Receptor Potential Channels / antagonists & inhibitors

Substances

  • Calcium Channels
  • Catechols
  • Fatty Alcohols
  • Nerve Tissue Proteins
  • TRPA1 Cation Channel
  • TRPA1 protein, human
  • TRPV Cation Channels
  • TRPV1 protein, human
  • Transient Receptor Potential Channels
  • gingerol