Dos Reis Rosa Franco Graziella, Fernandes Isabela Marie, de Souza Mikaela Lucinda, Gontijo Vanessa Silva, Alves Marina Amaral, de Souza Hygor Marcos Ribeiro, Do Invencio Carla Gabriely Gaião, Lontra Anna Carolina Pereira, de Paiva João Pedro Barros, Dos Santos Larissa Do Nascimento, da Silva Ana Clara Machado, Giorno Thaís Biondino Sardella, Guedes Isabella Alvim, Dardenne Laurent Emmanuel, Fernandes Patrícia Dias, Viegas Claudio
Laboratory of Research in Medicinal Chemistry - PeQuiM, Federal University of Alfenas, Institute of Chemistry, Alfenas, Brazil.
Laboratory of Metabolomics - LabMeta/LADETEC, Federal University of Rio de Janeiro, Institute of Chemistry, Rio de Janeiro, Brazil.
Future Med Chem. 2025 Jun;17(11):1229-1240. doi: 10.1080/17568919.2025.2515821. Epub 2025 Jun 16.
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 and 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 -acylaryl hydrazone analogues and their pharmacological evaluation for potential antioxidant, antinociceptive, and anti-inflammatory properties. Our results led to the identification of compounds (), with significant peripheral and central antinociceptive effects, (), and () with antinociceptive activities probably related to the ability of modulation of TRPV1 receptors, and () 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.
炎症是机体恢复细胞和组织稳态的保护机制。大麻二酚因其能够与内源性大麻素系统相关或不相关的多种受体结合而被报道，良好的安全性使其成为最有前途的用于治疗目的的植物大麻素之一。CBD已显示出显著降低细胞因子和其他炎症介质产生的能力，但其作用机制尚不清楚。在此，我们报告了一系列新型的八个萜烯-酰基芳基腙类似物的设计与合成及其潜在抗氧化、抗伤害感受和抗炎特性的药理学评价。我们的结果鉴定出具有显著外周和中枢抗伤害感受作用的化合物（）、具有可能与TRPV1受体调节能力相关的抗伤害感受活性的（）和（），以及似乎具有最有前途的外周抗伤害感受特征的（），其对福尔马林诱导的舔舐试验的神经源性和炎症阶段均显示出显著作用，并具有潜在的抗氧化活性。总体而言，我们的实验数据表明，基于CBD的新结构能够通过不同的作用方式确保外周和中枢抗伤害感受作用，且无体内毒性和适当的预测ADME性质。
