Elongation of the Hydrophobic Chain as a Molecular Switch:Discovery of Capsaicin Derivatives and Endogenous Lipids as Potent Transient Receptor Potential Vanilloid Channel 2 Antagonists
Schiano Moriello, Aniello
López Chinarro, Silvia
Novo Fernández, Olalla
Vitale, Rosa Maria
Di Marzo, Vincenzo
De Petrocellis, Luciano
MetadataShow full item record
The transient receptor potential vanilloid type-2 (TRPV2) protein is a nonselective Ca2+ permeable channel member of the TRPV subfamily, still considered an orphan TRP channel due to the scarcity of available selective and potent pharmacological tools and endogenous modulators. Here we describe the discovery of novel synthetic long-chain capsaicin derivatives as potent TRPV2 antagonists in comparison to the totally inactive capsaicin, the role of their hydrophobic chain, and how the structure-activity relationships of such derivatives led, through a ligand-based approach, to the identification of endogenous long-chain fatty acid ethanolamides or primary amides acting as TRPV2 antagonists. Both synthetic and endogenous antagonists exhibited differential inhibition against known TRPV2 agonists characterized by distinct kinetic profiles. These findings represent the first example of both synthetic and naturally occurring TRPV2 modulators with efficacy in the submicromolar/low-micromolar range, which will be useful for clarifying the physiopathological roles of this receptor, its regulation, and its targeting in pathological conditions.
Is part ofJournal of Medicinal Chemistry, 2018, vol. 61, núm. 18, p. 8255-8281
European research projects
Showing items related by title, author, creator and subject.
Combining a flow reactor with spray dryer to allow the preparation of food-grade quality sodium 2-polyhydroxyalkyl-1,3-thiazolidine-4-carboxylates with a low environmental impact Novo Fernández, Olalla; Balcells Fluvià, Mercè; Canela i Garayoa, Ramon; Eras i Joli, Jordi (Royal Society of Chemistry, 2016)The 1,3-thiazolidine-4-carboxylic acid (TCA) and 2-substituted 1,3-thiazolidine-4-carboxylic acids (2S-TCAs) are used as additive prodrugs of cysteine and glutathione in agronomy and in the food and pharmaceutical industries. ...
Eras i Joli, Jordi; Balcells Fluvià, Mercè; Canela i Garayoa, Ramon (Asociación de Químicos e Ingenieros del Instituto Químico de Sarriá, 2007)Glycidyl palmitate, used to obtain high purity monoglycerides and epoxy resins, can be obtained from glycerol using a two-step process. The first step of this new approach consists in a reaction of esterification-chlorination ...
Solarte Orozco, Carmen Eugenia; Escribà i Gelonch, Marc; Eras i Joli, Jordi; Villorbina Noguera, Gemma; Canela i Garayoa, Ramon; Balcells Fluvià, Mercè (Molecular Diversity Preservation International, 2011)The anticipated worldwide increase in biodiesel production will result in an accumulation of glycerol for which there are insufficient conventional uses. The surplus of this by-product has increased rapidly during the last ...