Structure-activity relationships of the ultrapotent vanilloid resiniferatoxin (RTX): the homovanillyl moiety.
Starting from ROPA (2), analogues of RTX (1a) modified on the acyl side chain were prepared and evaluated for vanilloid activity in HEK-293 cells over-expressing the human recombinant TRPV1. The ROPA motif provided an enhancement of potency sufficient to expand the range of vanillyl surrogates to structural elements (e.g., an unsubstituted phenyl ring) that afford inactive analogues in compounds from the capsaicin series.
Appendino
Giovanni
G
Dipartimento di Scienze Chimiche, Alimentari, Farmaceutiche e Farmacologiche, Università del Piemonte Orientale, Viale Ferrucci 33, 28100 Novara, Italy. appendino@pharm.unipmn.it
Ech-Chahad
Abdellah
A
Minassi
Alberto
A
Bacchiega
Sara
S
De Petrocellis
Luciano
L
Di Marzo
Vincenzo
V
D002478:Cells, Cultured; D004224:Diterpenes / Q000737:chemistry*; D006801:Humans; D018377:Neurotransmitter Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D050916:TRPV Cation Channels / Q000819:agonists*
D004224:Diterpenes; D018377:Neurotransmitter Agents; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; C487058:resiniferonol 9,13,14-ortho-phenylacetate; C024353:resiniferatoxin