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
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. ...
Genome-Wide Association Study of VKORC1 and CYP2C9 on acenocoumarol dose, stroke recurrence and intracranial haemorrhage in Spain Cullell, Natalia; Carrera, Caty; Muiño, Elena; Torres-Aguila, Nuria-Paz; Cárcel-Márquez, Jara; González-Sánchez, Jonathan; Gallego Fabrega, Cristina; Molina, Jessica; Besora, Sarah; Sotoca, Javier; Buongiorno, Maria-Teresa; Jiménez-Conde, Jordi; Giralt-Steinhauer, Eva; de Torres-Chacón, Reyes; Montaner, Joan; Mancha, Fernando; Cabezas, Juan A.; Martí Fàbregas, Joan; Prats Sánchez, Luis; Camps Renom, Pol; Purroy Garcia, Francisco; Cambray Carner, Serafí; Freijo, María del Mar; Vives-Bauzá, Cristòfol; Tur, Silvia; Font, Maria-Àngels; López-Cancio, Elena; Hernandez-Perez, Maria; Obach, Victor; Calleja, Ana; Arenillas, Juan; Rodríguez-Yáñez, Manuel; Castillo, José; Sobrino, Tomas; Fernández-Cádenas, Israel; Krupinski, Jerzy (Nature Publishing Group, 2020)Acenocoumarol is an oral anticoagulant with significant interindividual dose variations. Variants in CYP2C9 and VKORC1 have been associated with acenocoumarol maintenance dose. We analysed whether any of the 49 polymorphisms ...
Yara Varón, Edinson; Eras i Joli, Jordi; Torres i Grifo, Mercè; Sala i Martí, Núria; Villorbina Noguera, Gemma; Méndez, Jonh Jairo; Canela i Garayoa, Ramon (Elsevier, 2012)The ability of diverse commercial lipases and whole cells (fungal resting cells) to synthesise allyl and dichloropropyl acrylate from allyl dodecanoate through an interesterification process is presented. The process was ...