title: Chalcone Derivatives Activate and Desensitize the Transient Receptor Potential Ankyrin 1 Cation Channel, Subfamily A, Member 1 TRPA1 Ion Channel: Structure-Activity Relationships in vitro and Anti-Nociceptive and Anti-inflammatory Activity in vivo.
abstract: Eleven compounds belonging to the chalcone family were tested for their ability to activate and subsequently desensitize the rat transient receptor potential ankyrin 1 cation channel, subfamily A, member 1 (TRPA1) in a heterologous expression system. Four of the tested compounds were more potent than the TRPA1 agonist mustard oil, and showed also a strong desensitizing effect. Some chalcone compounds were not pungent in the eye-wiping assay and quite remarkably inhibited in a long-lasting and dose-dependent manner the pain response in the formalin test. Chalcones can be considered as novel candidates for the development of antihyperalgesic preparations based on TRPA1 desensitization.
authors.forename: Aniello Schiano
authors.initials: AS
authors.lastname: Moriello
authors.forename: Livio
authors.initials: L
authors.lastname: Luongo
authors.forename: Francesca
authors.initials: F
authors.lastname: Guida
authors.forename: Michael S
authors.initials: MS
authors.lastname: Christodoulou
authors.forename: Dario
authors.initials: D
authors.lastname: Perdicchia
authors.forename: Sabatino
authors.initials: S
authors.lastname: Maione
authors.forename: Daniele
authors.initials: D
authors.lastname: Passarella
authors.affiliation: vdimarzo@icb.cnr.it.
authors.forename: Vincenzo Di
authors.initials: VD
authors.lastname: Marzo
authors.affiliation: Endocannabinoid Research Group, Institute of Biomolecular Chemistry, National Research Council, Via Campi Flegrei 34, Comprensorio Olivetti, 80078 Pozzuoli, Naples, Italy. luciano.depetrocellis@icb.cnr.it.
authors.forename: Luciano De
authors.initials: L
authors.lastname: Petrocellis
mesh_terms: D000700:Analgesics / Q000737:chemistry* / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000627:therapeutic use*; D002118:Calcium / Q000378:metabolism; D047188:Chalcones / Q000737:chemistry / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde / Q000633:toxicity; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009149:Mustard Plant / Q000633:toxicity; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D010147:Pain Measurement; D010938:Plant Oils / Q000633:toxicity; D051381:Rats; D013329:Structure-Activity Relationship; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D047188:Chalcones; D010938:Plant Oils; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D005557:Formaldehyde; D002118:Calcium; C027793:mustard oil