Structural optimization and biological evaluation of 1,5-disubstituted pyrazole-3-carboxamines as potent inhibitors of human 5-lipoxygenase
文献类型：期刊论文
| 作者 | Zhou, Yu2 ; Liu, Jun3; Zheng, Mingyue2; Zheng, Shuli1,4; Jiang, Chunyi2; Zhou, Xiaomei1,4; Zhang, Dong2; Zhao, Jihui2; Ye, Deju2; Zheng, Mingfang2
|
| 刊名 | ACTA PHARMACEUTICA SINICA B
 |
| 出版日期 | 2016-01 |
| 卷号 | 6期号:1页码:32-45 |
| 关键词 | 5-Lipoxygenase 5-LOX inhibitors Pyrazole derivatives Leukotrienes-related diseases In vivo Benzo-fuse heterocyle Ischemic incults Brain inflammation |
| ISSN号 | 2211-3835 |
| DOI | 10.1016/j.apsb.2015.11.004 |
| 文献子类 | Article |
| 英文摘要 | Human 5-lipoxygenase (5-LOX) is a well-validated drug target and its inhibitors are potential drugs for treating leukotriene-related disorders. Our previous work on structural optimization of the hit compound 2 from our in-house collection identified two lead compounds, 3a and 3b, exhibiting a potent inhibitory profile against 5-LOX with IC50 values less than 1 mu mol/L in cell-based assays. Here, we further optimized these compounds to prepare a class of novel pyrazole derivatives by opening the fused ring system. Several new compounds exhibited more potent inhibitory activity than the lead compounds against 5-LOX. In particular, compound 4e not only suppressed lipopolysaccharide-induced inflammation in brain inflammatory cells and protected neurons from oxidative toxicity, but also significantly decreased infarct damage in a mouse model of cerebral ischemia. Molecular docking analysis further confirmed the consistency of our theoretical results and experimental data. In conclusion, the excellent in vitro and in vivo inhibitory activities of these compounds against 5-LOX suggested that these novel chemical structures have a promising therapeutic potential to treat leukotriene-related disorders. (C) 2016 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. |
| WOS关键词 | FOCAL CEREBRAL-ISCHEMIA ; DERIVATIVES ; DESIGN ; CYCLOOXYGENASE ; LEUKOTRIENES ; CELLS ; ACID |
| 资助项目 | National Natural Science Foundation of China[91229204] ; National Natural Science Foundation of China[81220108025] ; Major Project of Chinese National Programs for Fundamental Research and Development[2015CB910304] ; National High Technology Research and Development Program of China[2012AA020302] ; National Basic Research Program of China[2012CB518005] ; National S&T Major Projects[2012ZX09103101-072] ; National S&T Major Projects[2014ZX09507002-001] ; National S&T Major Projects[2013ZX09507-001] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:5625136 |
| WOS记录号 | WOS:000371987700004 |
| 出版者 | INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276238]  |
| 专题 | 药理学第三研究室 药物化学研究室 药理学第一研究室 |
| 通讯作者 | Liu, Dongxiang; Cheng, Jian; Liu, Hong |
| 作者单位 | 1.Soochow Univ, Inst Neurosci, Suzhou 215006, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China; 3.China Pharmaceut Univ, Nanjing 210009, Peoples R China; 4.Soochow Univ, Jiangsu Key Lab Translat Res & Therapy Neuropsych, Suzhou 215006, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Zhou, Yu,Liu, Jun,Zheng, Mingyue,et al. Structural optimization and biological evaluation of 1,5-disubstituted pyrazole-3-carboxamines as potent inhibitors of human 5-lipoxygenase[J]. ACTA PHARMACEUTICA SINICA B,2016,6(1):32-45. |
| APA | Zhou, Yu.,Liu, Jun.,Zheng, Mingyue.,Zheng, Shuli.,Jiang, Chunyi.,...&Liu, Hong.(2016).Structural optimization and biological evaluation of 1,5-disubstituted pyrazole-3-carboxamines as potent inhibitors of human 5-lipoxygenase.ACTA PHARMACEUTICA SINICA B,6(1),32-45. |
| MLA | Zhou, Yu,et al."Structural optimization and biological evaluation of 1,5-disubstituted pyrazole-3-carboxamines as potent inhibitors of human 5-lipoxygenase".ACTA PHARMACEUTICA SINICA B 6.1(2016):32-45. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。