Neuroactive and Anti-inflammatory Frankincense Cembranes: A Structure-Activity Study

Federica Pollastro, Samantha Golin, Giuseppina Chianese, Masteria Yunovilsa Putra, Aniello Schiano Moriello, Luciano De Petrocellis, Victor García, Eduardo Munoz, Orazio Taglialatela-Scafati, Giovanni Appendino

Risultato della ricerca: Contributo su rivistaArticolo in rivistapeer review

Abstract

An expeditious isolation method for the cembrane diterpene alcohols incensol (1a) and serratol (2) has been developed from respectively African and Indian frankincense. The two native alcohols and a series of semisynthetic derivatives of incensol were evaluated for transient receptor potential vanilloid 3 (TRPV3) activation and the inhibition of NF-κB, the putative molecular targets underlying the psychotropic and anti-inflammatory activities of incensol acetate (IA, 1b). Serratol (2) was the most potent TRPV3 activator, outperforming by 2 orders of magnitude the reference agonist thymol and by 1 order of magnitude incensol acetate (1b). Acylation, epimerization, and oxidation did not significantly improve the affinity of incensol for TRPV3, while NF-κB inhibition, marginal for both natural alcohols, could be improved by esterification of incensol (1a) with lipophilic acids. Interestingly, incensol (1a) but not IA (1b) was a potent inhibitor of STAT3, raising the possibility that hydrolysis to incensol (1a) might be involved in the in vivo biological activity of IA (1b). Serratol was not amenable to chemical modification, but some marine cembranoids related to the frankincense diterpenoids showed a certain degree of TRPV3-activating properties, qualifying the aliphatic macrocyclic cembrane skeleton as a selective chemotype to explore the pharmacology of TRPV3, a thermo-TRP otherwise resistant to modulation by small molecules.

Lingua originaleInglese
pagine (da-a)1762-1768
Numero di pagine7
RivistaJournal of Natural Products
Volume79
Numero di pubblicazione7
DOI
Stato di pubblicazionePubblicato - 22 lug 2016

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