2. Academic Validation
  3. New cannabidiol structure-related terpene N-acyl-hydrazones with potent antinociceptive and anti-inflammatory activity

New cannabidiol structure-related terpene N-acyl-hydrazones with potent antinociceptive and anti-inflammatory activity

  • Future Med Chem. 2025 Jun;17(11):1229-1240. doi: 10.1080/17568919.2025.2515821.
Graziella Dos Reis Rosa Franco 1,  Isabela Marie Fernandes 1,  Mikaela Lucinda de Souza 1,  Vanessa Silva Gontijo 1,  Marina Amaral Alves 2,  Hygor Marcos Ribeiro de Souza 2,  Carla Gabriely Gaião Do Invencio 3,  Anna Carolina Pereira Lontra 3,  João Pedro Barros de Paiva 3,  Larissa Do Nascimento Dos Santos 3,  Ana Clara Machado da Silva 3,  Thaís Biondino Sardella Giorno 3,  Isabella Alvim Guedes 4,  Laurent Emmanuel Dardenne 4,  Patrícia Dias Fernandes 3,  Claudio Viegas 1
Affiliations

Affiliations

  • 1 Laboratory of Research in Medicinal Chemistry - PeQuiM, Federal University of Alfenas, Institute of Chemistry, Alfenas, Brazil.
  • 2 Laboratory of Metabolomics - LabMeta/LADETEC, Federal University of Rio de Janeiro, Institute of Chemistry, Rio de Janeiro, Brazil.
  • 3 Laboratório de Farmacologia da dor e da inflamação, Federal University of Rio de Janeiro, Institute of Biomedical Sciences, Rio de Janeiro, Brazil.
  • 4 Grupo de Modelagem Molecular em Sistemas Biológicos - LNCC, National Laboratory for Scientific Computing, Petrópolis, Brazil.
PMID: 40521634 DOI: 10.1080/17568919.2025.2515821
Abstract

Inflammation is the organism's protective mechanism to restore cellular and tissue homeostasis. Cannabidiol has been reported for its ability to bind to diverse receptors related to or not related to the endocannabinoid system, with good safety being one of the most promising phytocannabinoids for therapeutical purposes. CBD has shown in vitro and in vivo ability to significantly reduce the production of cytokines and Other inflammatory mediators, with an unclear mechanism of action. Herein, we report the design and synthesis of a novel series of eight terpene N-acylaryl hydrazone analogues and their pharmacological evaluation for potential antioxidant, antinociceptive, and anti-inflammatory properties. Our results led to the identification of compounds 5a (PQM-242), with significant peripheral and central antinociceptive effects, 5b (PQM-243), and 5g (PQM-248) with antinociceptive activities probably related to the ability of modulation of TRPV1 receptors, and 5c (PQM-244) that seems to have the most promising peripheral antinociceptive profile, showing significant effects on both neurogenic and inflammatory phases of formalin-induced licking test, coupled to potential antioxidant activity. Overall, our experimental data suggest that the new CBD-based architecture is capable of ensuring peripheral and central antinociceptive effects by different modes of action, with no in vivo toxicity and adequate predicted ADME properties.

Keywords

CBD analogues; CBD-based N-acylhydrazone analogues; Cannabidiol; N-acyl-hydrazones; anti-inflammatory activity; antinociceptive activity.

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