Synthesis and evaluation of the anti-inflammatory activity of quinoline derivatives

Three types of quinoline derivatives, quinolin-2-one, 1-oxa-3,5-diaza-anthracen-6-one, and cyclopenta[a]anthracene, were designed and synthesized as potential anti-inflammatory agents. Their anti-inflammatory activities were evaluated using the xylene-induced ear-edema test in mice. Pharmacological analyses showed that compounds 3-(4-methyl-benzyl)-3,4,7,8-tetrahydro-2H,5H-1-oxa-3,5-diaza-anthracen-6-one (3g) and 9-(4-fluoro-phenyl)-5,8,9,10-tetrahydro-4H-7-oxa-2,3,9,11b-tetraaza-cyclopenta[a]anthracene (6d) exhibited the greatest anti-inflammatory activity (63.19 and 68.28 % inhibition, respectively, 30 min after intraperitoneal administration) and were more potent than the reference drug ibuprofen. The peak activity of 3g and 6d was observed 3 h after oral administration, and the compounds exhibited stronger anti-inflammatory activity than ibuprofen at 50 mg/kg at this time point. The most effective compound, 6d (hydrochloride salt), was evaluated in lipopolysaccharide (LPS)-stimulated RAW264.7 mouse macrophages, in which it significantly inhibited LPS-induced production of tumor necrosis factor-α and interleukin-6 in a dose-dependent manner.