Synthesis of resveratrol derivatives as new analgesic drugs through desensitization of the TRPA1 receptor

Bioorg Med Chem Lett. 2017 Jul 15;27(14):3167-3172. doi: 10.1016/j.bmcl.2017.05.025. Epub 2017 May 22.


A series of 31 resveratrol derivatives was designed, synthesized and evaluated for activation and inhibition of the TRPA1 channel. Most acted as activators and desensitizers of TRPA1 channels like resveratrol or allyl isothiocyanate (AITC). Compound 4z (HUHS029) exhibited higher inhibitory activity than resveratrol with an IC50 value of 16.1μM. The activity of 4z on TRPA1 was confirmed in TRPA1-expressing HEK293 cells, as well as in rat dorsal root ganglia neurons by a whole cell patch clamp recording. Furthermore, pretreatment with 4z exhibited an analgesic effect on AITC-evoked TRPA1-related pain behavior in vivo.

Keywords: Analgesic drug; HUHS029; Resveratrol; TRPA1.

MeSH terms

  • Analgesics / chemical synthesis*
  • Analgesics / pharmacology
  • Analgesics / therapeutic use
  • Animals
  • Calcium Channels / metabolism*
  • Ganglia, Spinal / drug effects
  • HEK293 Cells
  • Humans
  • Inhibitory Concentration 50
  • Nerve Tissue Proteins / agonists
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Nerve Tissue Proteins / metabolism*
  • Pain / drug therapy
  • Patch-Clamp Techniques
  • Rats
  • Resveratrol
  • Stilbenes / chemistry*
  • TRPA1 Cation Channel
  • Transient Receptor Potential Channels / agonists
  • Transient Receptor Potential Channels / antagonists & inhibitors
  • Transient Receptor Potential Channels / metabolism*


  • Analgesics
  • Calcium Channels
  • Nerve Tissue Proteins
  • Stilbenes
  • TRPA1 Cation Channel
  • TRPA1 protein, human
  • Transient Receptor Potential Channels
  • Resveratrol