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

doi:10.1002/cmdc.201500027

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	Inhibition of Neuroinflammation by Synthetic Androstene Derivatives Incorporating Amino Acid Methyl Esters on Activated BV-2 Microglia
	Wu, Jing 1; Du, Juanjuan 4; Gu, Ruinan 1; Zhang, Li 1; Zhen, Xuechu 1; Li, Yuanchao 4; Chen, Hongli2,3 ; Jiang, Biao2,3 ; Zheng, Longtai 1
	2015-04
发表期刊	CHEMMEDCHEM (IF:3.6[JCR-2023],3.5[5-Year])
ISSN	1860-7179
卷号	10 期号:4 页码:610-616
发表状态	已发表
DOI	10.1002/cmdc.201500027
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.
关键词	androstene derivatives microglia neuroinflammation neuroprotection
收录类别	SCI ; IC
语种	英语
资助项目	Jiangsu Science and Technology Commission[BY2011131]
WOS研究方向	Pharmacology & Pharmacy
WOS类目	Chemistry, Medicinal ; Pharmacology & Pharmacy
WOS记录号	WOS:000351773300004
出版者	WILEY-V C H VERLAG GMBH
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
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/2238
专题	免疫化学研究所免疫化学研究所_特聘教授组_抗体化学实验室
通讯作者	Wu, Jing
作者单位	1.Soochow Univ, Dept Pharmacol, Coll Pharmaceut Sci, Suzhou 215123, Peoples R China 2.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Organ Chem, Shanghai 200032, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, Med Chem, Shanghai 201203, 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.