title: 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.
authors.affiliation: School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing, Jiangsu, People's Republic of China ; Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, University Town, Wenzhou, Zhejiang, People's Republic of China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing, Jiangsu, People's Republic of China ; Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, University Town, Wenzhou, Zhejiang, People's Republic of China.
authors.forename: Chengguang
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, University Town, Wenzhou, Zhejiang, People's Republic of China.
authors.forename: Wenfei
authors.initials: W
authors.lastname: He
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, University Town, Wenzhou, Zhejiang, People's Republic of China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, University Town, Wenzhou, Zhejiang, People's Republic of China.
authors.forename: Qilu
authors.initials: Q
authors.lastname: Fang
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, University Town, Wenzhou, Zhejiang, People's Republic of China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xiao
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, University Town, Wenzhou, Zhejiang, People's Republic of China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, University Town, Wenzhou, Zhejiang, People's Republic of China.
authors.forename: Guang
authors.initials: G
authors.lastname: Liang
authors.affiliation: School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Shulin
authors.initials: S
authors.lastname: Yang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002478:Cells, Cultured; D003474:Curcumin / Q000031:analogs & derivatives* / Q000737:chemistry; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D004355:Drug Stability; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D020928:Mitogen-Activated Protein Kinases; D003474:Curcumin
keywords: anti-inflammation; inflammatory cytokines; quantitative structure–activity relationship; sepsis
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