The taming of capsaicin. Reversal of the vanilloid activity of N-acylvanillamines by aromatic iodination

Giovanni Appendino, Nives Daddario, Alberto Minassi, Aniello Schiano Moriello, Luciano De Petrocellis, Vincenzo Di Marzo

Risultato della ricerca: Contributo su rivistaArticolo in rivistapeer review

Abstract

Aromatic iodination ortho to the phenolic hydroxyl reverts the activity of the ultrapotent vanilloid agonist resiniferatoxin (RTX, 1a), generating the ultrapotent antagonist 5′-iodoRTX (1b). To better understand the role of iodine in this remarkable switch of activity, a systematic investigation on the halogenation of vanillamides, a class of compounds structurally simpler than resiniferonoids, was carried out. The results showed that (a) the antagonistic activity depends on the site of halogenation and is maximal at C-6′, (b) iodine is more efficient than chlorine and bromine at reverting the agonistic activity, and (c) iodine-carbon exchange decreases antagonist activity. Iodine-induced reversal of vanilloid activity was also observed in vanillamides more powerful than capsaicin, but a poor correlation was found between agonistic and antagonistic potencies, suggesting that differences exist in the way vanillamides and their 6′-iodo derivatives bind to TRPV1.″

Lingua originaleInglese
pagine (da-a)4663-4669
Numero di pagine7
RivistaJournal of Medicinal Chemistry
Volume48
Numero di pubblicazione14
DOI
Stato di pubblicazionePubblicato - 14 lug 2005

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