Synthesis and anti-inflammatory evaluation of novel mono-carbonyl analogues of curcumin in LPS-stimulated RAW 264.7 macrophages
Synthesis and anti-inflammatory evaluation of novel mono-carbonyl analogues of curcumin in LPS-stimulated RAW 264.7 macrophages
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LPS刺激的RAW 264.7巨噬细胞中新型姜黄素单羰基类似物的合成和抗炎评价
DOI：
10.1016/j.ejmech.2010.09.037
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发表时间：
2010-12-01
影响因子：
6.7
通讯作者：
Liang, Guang
中科院分区：
文献类型：
--
作者：
Zhao, Chengguang;Cai, Yuepiao;Liang, Guang
姜黄素是一种多功能的天然产物，对炎症具有调节作用。然而，姜黄素应用的一个主要限制是其生物利用度差。我们先前证明姜黄素的单羰基类似物具有改善的药代动力学特征。在这项研究中，合成了33种新的姜黄素单羰基类似物，并在LPS刺激的RAW 264.7巨噬细胞中评估了它们对TNF-α和IL-6释放的抑制作用。根据筛选数据进行定量构效关系分析，结果表明苯环上的吸电子基团有利于B类化合物的抗炎活性。此外，化合物AN 1和1382以剂量依赖性方式表现出抗炎能力。这些提高了这些化合物可能用作治疗炎性疾病的潜在药剂的可能性。(C)2010年Elsevier Masson SAS。All rights reserved.
Curcumin is a multifunctional natural product with regulatory effects on inflammation. However, a major limitation for the application of curcumin is its poor bioavailability. We previously demonstrated that the mono-carbonyl analogues of curcumin possessed improved pharmacokinetic profiles. In this study, 33 novel mono-carbonyl analogues of curcumin were synthesized and their inhibition against TNF-alpha and IL-6 release was evaluated in LPS-stimulated RAW 264.7 macrophages. Based on the screening data, quantitative structure activity relationship was conducted, indicating that electron-withdrawing groups in benzene ring are favourable to anti-inflammatory activities of B-class compounds. Furthermore, compounds AN1 and 1382 demonstrated anti-inflammatory abilities in a dose-dependent manner. These raise the possibility that these compounds might serve as potential agents for the treatment of inflammatory diseases. (C) 2010 Elsevier Masson SAS. All rights reserved.