Discovery and evaluation of asymmetrical monocarbonyl analogs of curcumin as anti-inflammatory agents

Abstract

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.

DOI: 10.2147/DDDT.S58168

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@inproceedings{Zhang2014DiscoveryAE, title={Discovery and evaluation of asymmetrical monocarbonyl analogs of curcumin as anti-inflammatory agents}, author={Yali Zhang and Chengguang Zhao and Wenfei He and Zhe Wang and Qilu Fang and Bing Xiao and Zhiguo Liu and Guang Liang and Shulin Yang}, booktitle={Drug design, development and therapy}, year={2014} }