title: Leucettamols, bifunctionalized marine sphingoids, act as modulators of TRPA1 and TRPM8 channels.
abstract: Leucettamols, bifunctionalized sphingoid-like compounds obtained from a marine sponge Leucetta sp., act as non-electrophilic activators of the TRPA1 channel and potent inhibitors of the icilin-mediated activation of the TRPM8 channel, while they are inactive on CB₁, CB₂ and TRPV1 receptors. Leucettamols represent the first compounds of marine origin to target TRPA1 and the first class of natural products to inhibit TRPM8 channels. The preparation of a small series of semi-synthetic derivatives revealed interesting details on the structure-activity relationships within this new chemotype of simple acyclic TRP modulators.
authors.affiliation: Department of Natural Compounds Chemistry, University of Naples Federico II, Via Montesano 49, 80131 Napoli, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Chianese
authors.forename: Ernesto
authors.initials: E
authors.lastname: Fattorusso
authors.forename: Masteria Yunovilsa
authors.initials: MY
authors.lastname: Putra
authors.forename: Barbara
authors.initials: B
authors.lastname: Calcinai
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bavestrello
authors.forename: Aniello Schiano
authors.initials: AS
authors.lastname: Moriello
authors.forename: Luciano
authors.initials: L
authors.lastname: De Petrocellis
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
authors.forename: Orazio
authors.initials: O
authors.lastname: Taglialatela-Scafati
mesh_terms: D000818:Animals; D057809:HEK293 Cells; D006801:Humans; D011161:Porifera / Q000737:chemistry*; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000187:drug effects / Q000378:metabolism; D013107:Sphingolipids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000187:drug effects* / Q000378:metabolism; D050053:TRPM Cation Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D050916:TRPV Cation Channels / Q000187:drug effects / Q000378:metabolism
chemical_list: D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D013107:Sphingolipids; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; D050053:TRPM Cation Channels; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; C480976:Trpa1 protein, rat; C498947:Trpm8 protein, rat; C540199:leucettamol A