Synthesis and optimization of novel allylated mono-carbonyl analogs of curcumin (MACs) act as potent anti-inflammatory agents against LPS-induced acute lung injury (ALI) in rats

被引：60

作者：

Zhu, Heping ^{[1
]}

Xu, Tingting ^{[1
,2
]}

Qiu, Chenyu ^{[1
]}

Wu, Beibei ^{[1
,2
]}

Zhang, Yali ^{[1
]}

Chen, Lingfeng ^{[1
]}

Xia, Qinqin ^{[1
]}

Li, Chenglong ^{[1
]}

Zhou, Bin ^{[2
]}

Liu, Zhiguo ^{[1
]}

Liang, Guang ^{[1
]}

机构：

[1] Wenzhou Med Univ, Sch Pharmaceut Sci, Chem Biol Res Ctr, 1210 Univ Town, Wenzhou 325035, Zhejiang, Peoples R China

[2] Wenzhou Med Univ, Affiliated Hosp 2, Wenzhou 325035, Zhejiang, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2016年 / 121卷

关键词：

Acute lung injury; Water solubility; Chemical stability; Drug design; Mono-carbonyl analogs of curcumin; MURINE MODEL; INTERLEUKIN-6; INFLAMMATION; CELLS;

D O I：

10.1016/j.ejmech.2016.05.041

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel symmetric and asymmetric allylated mono-carbonyl analogs of curcumin (MACs) were synthesized using an appropriate synthetic route and evaluated experimentally thru the LPS-induced expression of TNF-alpha and IL-6. Most of the obtained compounds exhibited improved water solubility as a hydrochloride salt compared to lead molecule 8f. The most active compound 7a was effective in reducing the Wet/Dry ratio in the lungs and protein concentration in bronchoalveolar lavage fluid. Meanwhile, 7a also inhibited mRNA expression of several inflammatory cytokines, including TNF-alpha, IL-6, IL-1 beta, and VCAM-1, in Beas-2B cells after Lipopolysaccharide (LPS) challenge. These results suggest that 7a could be therapeutically beneficial for use as an anti-inflammatory agent in the clinical treatment of acute lung injury (ALI). (C) 2016 Elsevier Masson SAS. All rights reserved.

引用

页码：181 / 193

页数：13

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