| Three types of derivatives quinolin-2-one, 1-oxa-3,5-diaza-anthracen-6-one, and cyclopenta[a]anthracene were designed and synthesized, on the principles of hybridization, as potential anti-inflammatory agents. Their anti-inflammatory activities were evaluated by xylene-induced ear-edema test in mice. Pharmacological analyses showed that most compounds exhibited modest anti-inflammatory activities. Especially,3-(4-methyl-benzyl)-3,4,7,8-tetrahydro-2H;5H-1-oxa-3,5-diaza-anthracen-6-one (3g) and (9-(4-fluoro-pheny1)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), which was more potent than the reference drug, ibuprofen. The peak activity of 3g and 6d was observed 3 h after oral administration, and they exhibited stronger anti-inflammatory activity than ibuprofen at 50 mg/kg at the peak time. The most potent compound,6d (hydrochloride salt) was evaluated in a lipopolsaccharide (LPS)-induced mouse RAW 264.7 macrophage test. This compound inhibited the LPS-induced production of tumor necrosis factor-a and interleukin-6 significantly in a dose-dependent manner. |
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