Synthesis and biological evaluation of novel sinomenine derivatives as anti-inflammatory agents
Synthesis and biological evaluation of novel sinomenine derivatives as anti-inflammatory agents
复制标题
新型抗炎青藤碱衍生物的合成及生物学评价
DOI：
10.1016/j.ejmech.2012.01.036
复制
发表时间：
2012-04-01
影响因子：
6.7
通讯作者：
Li, Jian-Xin
中科院分区：
文献类型：
--
作者：
Teng, Peng;Liu, Hai-Liang;Li, Jian-Xin
青藤碱（1）临床上可用于治疗类风湿性关节炎（RA），但其疗效相当弱。本研究设计并合成了基于青藤碱的新型同二聚体和可变长度连接体单体库，并利用RAW 264. 7细胞和小鼠评价了它们的生物活性。在这些化合物中，2f和3b对一氧化氮（NO）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的产生具有比1强得多的抑制作用。初步机制研究表明，3 B特异性抑制核因子-κ B（NF-κ B B）信号通路，2 f同时抑制NF-κ B和丝裂原活化蛋白激酶（MAPK）信号通路。此外，3b和2f显着减轻脂多糖（LPS）诱导的死亡率。这两种化合物可能作为抗炎药物发现的有价值的候选者。(C)2012年Elsevier Masson SAS。All rights reserved.
Sinomenine (1) is clinically available for the treatment of rheumatoid arthritis (RA), however, its efficacy is quite weak. In the present study, a library of novel sinomenine-based homodimers and monomers through variable-length linkers were designed and synthesized, and their bioactivities were evaluated using RAW264.7 cells and mice. Among the compounds, 2f and 3b possessed much more potent inhibitory effects on the production of nitric oxide (NO), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) than 1. Preliminary mechanism investigation revealed that 3b inhibited nuclear factor-kappa B (NF-kappa B) signaling pathway specifically, 2f suppressed both NF-kappa B and mitogen-activated protein kinase (MAPK) cascades. Moreover, 3b and 2f significantly alleviated the lipopolysaccharide (LPS)-induced mortality. These two compounds might serve as valuable candidates for anti-inflammatory drug discovery. (C) 2012 Elsevier Masson SAS. All rights reserved.