Biological Activity
ki: 8.5 nm4-quinolone-3-carboxamide furan cb2 agonist is a high-affinity ligand of cb2.the endocannabinoid system consists of endogenous cannabinoids (endocannabinoids), cannabinoid receptors (primarily cb1 and cb2), and the enzymes that synthesize and degrade endocannabinoids.
in vitro
previous study found that 4-quinolone-3-carboxamide furan cb2 agonist (4g) was devoid of any potential “indirect” agonist activity at cannabinoid receptors, exerted by prolonging the lifespan of endocannabinoids because 4g at up to a 10 μm concentration did not inhibit anandamide or 2-ag degradation by faah or magl, respectively. in cytotosicity study, 4g was tested at 1 μm and the results showed that it exhibited very low or no cytotoxicity, the cell viability being above 95% after a 72 h treatment [1].
in vivo
in animal study, 4g was found to have antinociceptive activity in the formalin test in mice. moreover, 4g was very potent with maximal effect being reached at the 1 mg/kg dose and efficacious also on the first phase of the nocifensive response. the effect of 4g could be strongly reduced by the addition of am630, a cb2-selective antagonist/inverse agonist, therefore demonstrating that 4g might act as a potent and selective cb2 agonist [1].
References
[1] s. pasquini, m. de rosa, v. pedani, et al. investigations on the 4-quinolone-3-carboxylic acid motif. 4. identification of new potent and selective ligands for the cannabinoid type 2 receptor with diverse substitution patterns and antihyperalgesic effects in mice. journal of medicinal chemistry 54, 5444-5453 (2011).
