Synthesis and evaluation of the anti-inflammatory activity of quinoline derivatives
Synthesis and evaluation of the anti-inflammatory activity of quinoline derivatives
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DOI：
10.1007/s00044-015-1323-y
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发表时间：
2015-01
影响因子：
2.6
通讯作者：
Xiang Wen;Shiben Wang;Dachuan Liu;Guo-Hua Gong;Zhe-Shan Quan
中科院分区：
文献类型：
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作者：
Xiang Wen;Shiben Wang;Dachuan Liu;Guo-Hua Gong;Zhe-Shan Quan
设计并合成了喹啉衍生物喹啉-2- 1、1-氧-3,5-二氮杂蒽-6- 1和环五[a]蒽作为潜在的抗炎剂。用二甲苯致小鼠耳水肿试验评价其抗炎活性。药理分析表明，化合物3-（4-甲基苄基）-3,4,7,8-四氢- 2h， 5h -1-氧-3,5-二氮杂-蒽-6- 1 （3g）和9-（4-氟苯基）-5,8,9,10-四氢- 4h -7-氧-2,3,9,11b-四氮杂-环五[a]蒽（6d）表现出最大的抗炎活性（腹腔给药30 min后分别抑制63.19%和68.28%），比对照药物布洛芬更有效。3和6的抗炎活性在给药后3 h达到峰值，且抗炎活性强于50mg /kg剂量的布洛芬。最有效的化合物6d（盐酸盐）在脂多糖（LPS）刺激的RAW264.7小鼠巨噬细胞中进行了评估，其显著抑制LPS诱导的肿瘤坏死因子-α和白细胞间素-6的产生，并呈剂量依赖性。
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 of3gand6dwas 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.