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

被引：0
作者：
Xiang Wen
Shi-Ben Wang
Da-Chuan Liu
Guo-Hua Gong
Zhe-Shan Quan
机构：
[1] Yanbian University College of Pharmacy,Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education
[2] Inner Mongolia University for the Nationalities,Medicinal Chemistry and Pharmacology Institute
来源：
Medicinal Chemistry Research | 2015年 / 24卷
关键词：
Anti-inflammatory; IL-6 inhibition; Mannich reaction; Quinoline; Synthesis; TNF-α;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
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.
引用
收藏
页码：2591 / 2603
页数：12
相关论文
共 116 条
[1]  
Abdel-Aziz M(2013)New nitric oxide donating 1,2,4-triazole/oxime hybrids: synthesis, investigation of anti-inflammatory, ulceroginic liability and antiproliferative activities Bioorg Med Chem 21 3839-3849
[2]  
Abuo-Rahma Gel D(2014)1,2,4-Triazole/oxime hybrids as new strategy for nitric oxide donors: synthesis, anti-inflammatory, ulceroginicity and antiproliferative activities Eur J Med Chem 71 185-198
[3]  
Beshr EA(2000)Lipopolysaccharide-induced lung injury in mice. I. Concomitant evaluation of inflammatory cells and haemorrhagic lung damage Pulm Pharmacol Ther 13 61-69
[4]  
Ali TF(2007)A new enantiodivergent synthesis of the geissman–waiss lactone Tetrahedron 63 4278-4283
[5]  
Abuo-Rahma Gel D(2006)Efficacy and safety of over-the-counter analgesics in the treatment of common cold and flu J Clin Pharm Ther 31 309-319
[6]  
Abdel-Aziz M(2009)Design and synthesis of azolopyrimidoquinolines, pyrimidoquinazolines as anti-oxidant, anti-inflammatory and analgesic activities Eur J Med Chem 44 609-624
[7]  
Beshr EA(2008)Synthesis and anticonvulsant activity of 5-phenyl-[1,2,4]-triazolo[4,3- Arch Pharm 341 774-779
[8]  
Ali TF(1995)]quinolines Am J Respir Crit Care Med 151 293-301
[9]  
Asti C(1996)Clinical risks for development of the acute respiratory distress syndrome Res Immunol 147 417-434
[10]  
Ruggieri V(2004)Inflammation: patterns and new concepts J Chin Med Assoc 67 442-446
12345678910