Microfluidics assisted synthesis and bioevaluation of sinomenine derivatives as antiinflammatory agents
Microfluidics assisted synthesis and bioevaluation of sinomenine derivatives as antiinflammatory agents
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DOI：
10.1016/j.ejmech.2012.12.051
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发表时间：
2013-04-01
影响因子：
6.7
通讯作者：
Li, Jian-Xin
中科院分区：
文献类型：
--
作者：
Jin, Jie;Teng, Peng;Li, Jian-Xin
青藤碱(1)目前在我国用于治疗类风湿性关节炎(RA)，其疗效仍有提升空间。在本研究中，基于毛细管的微流体系统被有效地应用于两个新型青藤碱衍生物系列的合成。与间歇式反应相比，微反应器中的 Heck 反应的转化率要高得多。微反应器两步合成异恶唑啉大大缩短了反应时间，且无需任何中间体分离。体外评估了合成化合物对 TNF-α 诱导的核因子 kappa B (NF-kappa B) 激活的抑制活性。在这些化合物中，3c和3g显示出有效的抑制活性。此外，3g在体内表现出抗炎作用。 (C) 2013 Elsevier Masson SAS。所有紧身衣均保留。
Sinomenine (1) is currently used for the treatment of rheumatoid arthritis (RA) in China and there is still room for the improvement of its efficacy. In present study, capillary based microfluidic system was effectively applied for the syntheses of two novel series of sinomenine derivatives. The Heck reactions in microreactor gave much higher conversions compared to the batch ones. The two-step synthesis of the isoxazoline in microreactor greatly shortened the reaction time without any isolation of intermediates. The inhibitory activity of synthesized compounds on the TNF-alpha-induced nuclear factor kappa B (NF-kappa B) activation was evaluated in vitro. Among the compounds, 3c and 3g showed the potent inhibitory activity. Furthermore, 3g exhibited the antiinflammatory effect in vivo. (C) 2013 Elsevier Masson SAS. All tights reserved.