Details

Autor(en) / Beteiligte

• Serafini, Marta
• Griglio, Alessia
• Aprile, Silvio
• Seiti, Fabio
• Travelli, Cristina
• Pattarino, Franco
• Grosa, Giorgio
• Sorba, Giovanni
• Genazzani, Armando A
• Gonzalez-Rodriguez, Sara
• Butron, Laura
• Devesa, Isabel
• Fernandez-Carvajal, Asia
• Pirali, Tracey
• Ferrer-Montiel, Antonio

Titel

Targeting Transient Receptor Potential Vanilloid 1 (TRPV1) Channel Softly: The Discovery of Passerini Adducts as a Topical Treatment for Inflammatory Skin Disorders

Ist Teil von

• Journal of medicinal chemistry, 2018-05, Vol.61 (10), p.4436-4455

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Despite being an old molecule, capsaicin is still a hot topic in the scientific community, and the development of new capsaicinoids is a promising pharmacological approach in the management of skin disorders related to inflammation and pruritus. Here we report the synthesis and the evaluation of capsaicin soft drugs that undergo deactivation by the hydrolyzing activity of skin esterases. The implanting of an ester group in the lipophilic moiety of capsaicinoids by the Passerini multicomponent reaction affords both agonists and antagonists that retain transient receptor potential vanilloid 1 channel (TRPV1) modulating activity and, at the same time, are susceptible to hydrolysis. The most promising antagonist identified shows in vivo anti-nociceptive activity on pruritus and hyperalgesia without producing hyperthermia, thus validating it as novel treatment for dermatological conditions that implicate TRPV1 channel dysfunction.