Synthesis and biological evaluation of unique stereodimers of sinomenine analogues as potential inhibitors of NO production

被引：36

作者：

Teng, Peng ^{[1
]}

Liu, Hai-Liang ^{[2
]}

Deng, Zhang-Shuang ^{[1
]}

Shi, Zhi-Bing ^{[1
]}

He, Yun-Mian ^{[1
]}

Feng, Li-Li ^{[2
]}

Xu, Qiang ^{[2
]}

Li, Jian-Xin ^{[1
]}

机构：

[1] Nanjing Univ, Sch Chem & Chem Engn, Key Lab Analyt Chem Life Sci, Nanjing 210093, Peoples R China

[2] Nanjing Univ, Sch Life Sci, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2011年 / 19卷 / 10期

基金：

中国国家自然科学基金;

关键词：

Sinomenine; Stereodimer; Inhibitor; Nitric oxide; iNOS; NITRIC-OXIDE SYNTHASE; (+)-MORPHINAN SERIES; DIMERIZATION; MACROPHAGES; EXPRESSION; ARTHRITIS; MODELS; GENE; RATS;

D O I：

10.1016/j.bmc.2011.04.006

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Inhibition of the excessive NO production has been recognized as a potential means for the treatment of rheumatoid arthritis (RA). In order to discover more potent inhibitors and explore the preliminary structure activity relationship, a series of unique stereodimers of sinomenine analogues were designed and synthesized. Their inhibitory activity on NO production and cytotoxicity were evaluated using LPS-activated murine macrophages RAW264.7 assay and MTT method, respectively. Among these compounds, 1a, 2, 2a, 2b, and 4 showed potent inhibitory activity on NO production without obvious cytotoxicity. Furthermore, 2, 2a, and 2b significantly suppressed mRNA expression of iNOS. Interestingly, (S)-dimers displayed a better bioactivity than (R)-dimers. These compounds may sever as lead candidates in the development of novel therapeutic drugs for RA treatment. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：3096 / 3104

页数：9

共 41 条

[1]

A versatile synthetic dimerizer for the regulation of protein-protein interactions [J].