title: Synthesis and biological evaluation of [6]-gingerol analogues as transient receptor potential channel TRPV1 and TRPA1 modulators.
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).
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, Roma, Italy. enrico.morera@uniroma1.it
authors.forename: Enrico
authors.initials: E
authors.lastname: Morera
authors.forename: Luciano
authors.initials: L
authors.lastname: De Petrocellis
authors.forename: Ludovica
authors.initials: L
authors.lastname: Morera
authors.forename: Aniello Schiano
authors.initials: AS
authors.lastname: Moriello
authors.forename: Marianna
authors.initials: M
authors.lastname: Nalli
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
authors.forename: Giorgio
authors.initials: G
authors.lastname: Ortar
mesh_terms: D015220:Calcium Channels; D002396:Catechols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005233:Fatty Alcohols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009419:Nerve Tissue Proteins / Q000819:agonists* / Q000037:antagonists & inhibitors; D011485:Protein Binding / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels / Q000819:agonists* / Q000037:antagonists & inhibitors; D050051:Transient Receptor Potential Channels / Q000819:agonists* / Q000037:antagonists & inhibitors
chemical_list: D015220:Calcium Channels; D002396:Catechols; D005233:Fatty Alcohols; D009419:Nerve Tissue Proteins; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D050051:Transient Receptor Potential Channels; C007845:gingerol