Inhibition of Neuroinflammation by Synthetic Androstene Derivatives Incorporating Amino Acid Methyl Esters on Activated BV-2 Microglia

doi:10.1002/cmdc.201500027

	Inhibition of Neuroinflammation by Synthetic Androstene Derivatives Incorporating Amino Acid Methyl Esters on Activated BV-2 Microglia
	Wu, Jing 4; Du, Juanjuan 2; Gu, Ruinan 4; Zhang, Li 4; Zhen, Xuechu 4; Li, Yuanchao 2; Chen, Hongli 1,3; Jiang, Biao 1,3; Zheng, Longtai 4
刊名	CHEMMEDCHEM
	2015-04
卷号	10 期号:4 页码:610-616
关键词	androstene derivatives microglia neuroinflammation neuroprotection
ISSN号	1860-7179
DOI	10.1002/cmdc.201500027
文献子类	Article
英文摘要	Androstene derivatives incorporating amino acid methyl esters were prepared, and their anti-inflammatory effects were evaluated in lipopolysaccharide (LPS)-activated BV-2 microglial cells. Several compounds exhibited dose-dependent inhibition. The most active compound, methyl ((3S,10R,13S)-3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-17-carbonyl)-L-phenylalaninate (10) significantly suppressed LPS-induced expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor- (TNF-). Mechanistic studies revealed that compound 10 markedly inhibits phosphorylation of p38 mitogen-activated protein kinases (MAPKs) and subsequent transcription factor (NF-B) and activator protein-1 (AP-1) activation. Furthermore, compound 10 decreased LPS-activated microglial neurotoxicity in a condition medium/HT-22 neuroblastoma co-culture model. Taken together, these results suggest 10 is a potential lead compound for the development of a novel therapeutic agent for neurodegenerative diseases.
资助项目	National Science Foundation of China[21102167] ; National Science Foundation of China[81130023] ; National Science Foundation of China[81372688] ; Ministry of Science and Technology of China[2009CB522000] ; Ministry of Science and Technology of China[2011CB5C4403] ; Priority Academic Program Development of Jiangsu Higher Education Institutes (PAPD)[00000000] ; Jiangsu Science and Technology Commission[BY2011131]
WOS关键词	NITRIC-OXIDE SYNTHASE ; FACTOR-ALPHA GENE ; NF-KAPPA-B ; PARKINSONS-DISEASE ; ALZHEIMERS-DISEASE ; OXIDATIVE STRESS ; PROTEIN-KINASES ; NO PRODUCTION ; INFLAMMATION ; EXPRESSION
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	WILEY-V C H VERLAG GMBH
WOS记录号	WOS:000351773300004
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276591]
专题	药物化学研究室
通讯作者	Wu, Jing
作者单位	1.Chinese Acad Sci, Shanghai Inst Organ Chem, Shanghai 200032, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Med Chem, Shanghai 201203, Peoples R China 3.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China; 4.Soochow Univ, Dept Pharmacol, Coll Pharmaceut Sci, Suzhou 215123, Peoples R China;
推荐引用方式 GB/T 7714	Wu, Jing,Du, Juanjuan,Gu, Ruinan,et al. Inhibition of Neuroinflammation by Synthetic Androstene Derivatives Incorporating Amino Acid Methyl Esters on Activated BV-2 Microglia[J]. CHEMMEDCHEM,2015,10(4):610-616.
APA	Wu, Jing.,Du, Juanjuan.,Gu, Ruinan.,Zhang, Li.,Zhen, Xuechu.,...&Zheng, Longtai.(2015).Inhibition of Neuroinflammation by Synthetic Androstene Derivatives Incorporating Amino Acid Methyl Esters on Activated BV-2 Microglia.CHEMMEDCHEM,10(4),610-616.
MLA	Wu, Jing,et al."Inhibition of Neuroinflammation by Synthetic Androstene Derivatives Incorporating Amino Acid Methyl Esters on Activated BV-2 Microglia".CHEMMEDCHEM 10.4(2015):610-616.