Discovery and evaluation of asymmetrical monocarbonyl analogs of curcumin as anti-inflammatory agents.
Discovery and evaluation of asymmetrical monocarbonyl analogs of curcumin as anti-inflammatory agents.
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姜黄素不对称单羰基类似物作为抗炎剂的发现和评价
DOI：
10.2147/dddt.s58168
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Yang S
中科院分区：
文献类型：
--
作者：
Zhang Y;Zhao C;He W;Wang Z;Fang Q;Xiao B;Liu Z;Liang G;Yang S
脓毒症是一种全身性炎症反应综合征，主要由革兰氏阴性菌细胞壁的一种成分脂多糖（LPS）通过Toll样受体4-丝裂原活化蛋白激酶/核因子-κ B依赖的促炎信号通路引起。本文合成了26个姜黄素的不对称单羰基类似物，并通过抑制LPS诱导的小鼠RAW 264. 7巨噬细胞分泌肿瘤坏死因子-α和白细胞介素-6来评价其抗炎活性。5个活性化合物（3a、3c、3d、3 j和3l）对肿瘤坏死因子-α和白细胞介素-6的释放表现出剂量依赖性的抑制作用，并且它们在体外也表现出比姜黄素高得多的化学稳定性。类似物3a和3c的抗炎活性可能与它们抑制细胞外信号调节激酶的磷酸化和核因子-κ B的活化有关。此外，3c在体内表现出对LPS诱导的脓毒性死亡的显著保护。这些结果表明，不对称单羰基姜黄素类似物可用作治疗急性炎症性疾病的候选物。
Sepsis is a systemic inflammatory response syndrome and is mainly caused by lipopolysaccharides (LPS) – a component of the cell walls of gram-negative bacteria, via toll-like receptor 4–mitogen-activated protein kinases/nuclear factor-kappa B-dependent proinflammatory signaling pathway. Here, we synthesized 26 asymmetric monocarbonyl analogs of curcumin and evaluated their anti-inflammatory activity by inhibiting the LPS-induced secretion of tumor necrosis factor-α and interleukin-6 in mouse RAW264.7 macrophages. Five active compounds (3a, 3c, 3d, 3j, and 3l) exhibited dose-dependent inhibition against the release of tumor necrosis factor-α and interleukin-6, and they also showed much higher chemical stability than curcumin in vitro. The anti-inflammatory activity of analogs 3a and 3c may be associated with their inhibition of the phosphorylation of extracellular signal-regulated kinase and the activation of nuclear factor-kappa B. In addition, 3c exhibited significant protection against LPS-induced septic death in vivo. These results indicate that asymmetrical monocarbonyl curcumin analogs may be utilized as candidates for the treatment of acute inflammatory diseases.