2. Academic Validation
  3. Synthetic bioactive olivetol-related amides: The influence of the phenolic group in cannabinoid receptor activity

Synthetic bioactive olivetol-related amides: The influence of the phenolic group in cannabinoid receptor activity

  • Bioorg Med Chem. 2020 Jun 1;28(11):115513. doi: 10.1016/j.bmc.2020.115513.
Antonella Brizzi 1,  Francesca Aiello 2,  Serena Boccella 3,  Maria Grazia Cascio 4,  Luciano De Petrocellis 5,  Maria Frosini 6,  Francesca Gado 7,  Alessia Ligresti 5,  Livio Luongo 3,  Pietro Marini 4,  Claudia Mugnaini 8,  Federica Pessina 9,  Federico Corelli 8,  Sabatino Maione 3,  Clementina Manera 7,  Roger G Pertwee 4,  Vincenzo Di Marzo 5
Affiliations

Affiliations

  • 1 Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via A. Moro 2, 53100 Siena, Italy. Electronic address: [email protected].
  • 2 Dipartimento di Farmacia e Scienze della Salute e della Nutrizione, Università della Calabria, 87036 Arcavacata di Rende, Cosenza, Italy.
  • 3 Dipartimento di Medicina Sperimentale, Divisione di Farmacologia, Università degli Studi della Campania "L. Vanvitelli", Via Santa Maria di Costantinopoli 16, 80138 Napoli, Italy.
  • 4 School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB252ZD, Scotland, UK.
  • 5 Endocannabinoid Research Group, Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Via Campi Flegrei 34, 80078 Pozzuoli (Napoli), Italy.
  • 6 Dipartimento di Scienze della Vita, Università degli Studi di Siena, Via A. Moro 2, 53100 Siena, Italy.
  • 7 Dipartimento di Farmacia, Università di Pisa, Via Bonanno Pisano 6, 56126 Pisa, Italy.
  • 8 Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via A. Moro 2, 53100 Siena, Italy.
  • 9 Dipartimento di Medicina Molecolare e dello Sviluppo, Università degli Studi di Siena, Via A. Moro 2, 53100 Siena, Italy.
PMID: 32340793 DOI: 10.1016/j.bmc.2020.115513
Abstract

Focusing on the importance of the free phenolic hydroxyl moiety, a family of 23 alkylresorcinol-based compounds were developed and evaluated for their Cannabinoid Receptor binding properties. The non-symmetrical hexylresorcinol derivative 29 turned out to be a CB2-selective competitive antagonist/inverse agonist endowed with good potency. Both the olivetol- and 5-(2-methyloctan-2-yl)resorcinol-based derivatives 23 and 24 exhibited a significant antinociceptive activity. Interestingly, compound 24 proved to be able to activate both cannabinoid and TRPV1 receptors. Even if Cannabinoid Receptor subtype selectivity remained a goal only partially achieved, results confirm the validity of the alkylresorcinol nucleus as skeleton for the identification of potent Cannabinoid Receptor modulators.

Keywords

Alkylresorcinols; Antinociceptive effect; Cannabinoid ligands; Dual ligand; Endocannabinoids; Transient receptor potential vanilloid type-1 channel.

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