New synthetic structural analogues of cannabidiol and its anti-inflammatory potential for the treatment of inflammatory diseases

Introduction: Inflammation is involved in the pathophysiological process of several diseases such as inflammatory bowel diseases, COVID-19 and certain types of cancer. As cannabidiol (CBD) has already known anti-inflammatory properties, synthetic structural analogues of CBD were synthesized to explore its effects in preclinical models of acute inflammation [1, 2].

Methods: Female Swiss Webster mice (n=6-8) were used in model of carrageenan-induced cell migration into the subcutaneous air pouch (SAP). Treatment was realized orally with PQM-275 or PQM-276 (1, 3 or 10 µmol/kg) 24h before the carrageenan injection into the SAP. Exsudate were collect for leukocyte count and cytokine measurement. Statistical analysis was performed by ANOVA followed by Dunnett´s test (*p<0.05).

Results: PQMs reduced leukocyte migration at 3 doses tested. Saline-Vehicle: 3.4± 3.7 x10³cel/µL; Dexamethasone (6,5 µmol/kg): 53.5±17.5 x10³cel/µL; Carrageenan-Vehicle: 157.3±71.4x10³cel/µL; PQM-275: 1, 3 and 10 µmol/kg: 84.6±45.8*x10³ cel/µL; 71.6±44*x10³ cel/µL; 52.4±36.5*x10³ cel/µL respectively; PQM-276:1, 3 and 10 µmol/kg: 76.3±28.7*x10³ cel/µL; 59.0±32.4*x10³ cel/µL; 71.6±24.6*x10³ cel/µL respectively. PQMs also reduced TNF-α levels at 3 doses tested. Saline-Vehicle: 70.7±17.8 pg/mL; Carrageenan-Vehicle: 330.3±97.4 pg/mL; Dexamethasone (6,5 µmol/kg): 104±37.5 pg/mL; PQM-275: 1 µmol/kg: 225.8±58.8* pg/mL; 3 µmol/kg: 229.7±82.4* pg/mL; 10 µmol/kg: 128±33.4* pg/mL; PQM-276: 1 µmol/kg: 153.8±80.9* pg/mL; 3 µmol/kg: 143.7±39.7* pg/mL; 10 µmol/kg: 143.2±44.4* pg/mL. Both substances showed significant effects at preclinical models of acute inflammation, suggesting its anti-inflammatory potential.

References: 1. Int. Immunol. (2021) 33:127; 2. Antioxidants. (2019) 9:21.

Financial Support: CAPES, CNPq and FAPERJ.