Synthesis and Anti-Inflammatory Evaluation of Novel C66 Analogs for the Treatment of LPS-Induced Acute Lung Injury
Synthesis and Anti-Inflammatory Evaluation of Novel C66 Analogs for the Treatment of LPS-Induced Acute Lung Injury
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用于治疗 LPS 引起的急性肺损伤的新型 C66 类似物的合成和抗炎评价
DOI：
10.1111/cbdd.12548
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发表时间：
2015-10-01
影响因子：
3
通讯作者：
Liang, Guang
中科院分区：
文献类型：
--
作者：
Feng, Jianpeng;Xiao, Bing;Liang, Guang
我们以前报道了一个对称的单羰基类似物姜黄素（MACs），C66，它表现出潜在的抗炎活性和低毒性。在继续我们正在进行的研究中，我们设计并合成了34个基于C66作为先导分子的不对称MAC。大多数C66类似物有效抑制LPS诱导的TNF-和IL-6表达。此外，还进行了初步SAR。此外，发现活性化合物4a 11和4a 16有效地降低肺中的W/D比和支气管肺泡灌洗液（BALF）中的蛋白质浓度。同时，组织病理学检查表明，这两个类似物显着减轻LPS诱导的ALI大鼠肺组织损伤。4a 11和4a 16还可抑制LPS刺激后Beas-2B细胞TNF-α、IL-6、IL-1、考克斯-2、ICAM-1和VCAM-1的mRNA表达。总之，这些数据显示了一系列新的C66类似物作为治疗LPS诱导的ALI的有前途的抗炎剂。
We previously reported a symmetric monocarbonyl analog of curcumin (MACs), C66, which demonstrated potential anti-inflammatory activity and low toxicity. In continuation of our ongoing research, we designed and synthesized 34 asymmetric MACs based on C66 as a lead molecule. A majority of the C66 analogs effectively inhibited LPS induction of TNF- and IL-6 expression. Additionally, a preliminary SAR was conducted. Furthermore, active compounds 4a11 and 4a16 were found to effectively reduce theW/D ratio in the lungs and the protein concentration in the bronchoalveolar lavage fluid (BALF). Meanwhile, a histopathological examination indicated that these two analogs significantly attenuate tissue injury in the lungs with LPS-induced ALI rats. 4a11 and 4a16 also inhibited mRNA expression of several inflammatory cytokines, including TNF-, IL-6, IL-1, COX-2, ICAM-1 and VCAM-1, in the Beas-2B cellsafter LPS challenge. Altogether, the data exhibit a series of new C66 analogs as promising anti-inflammatory agents for the treatment of LPS-induced ALI.