Discovery and evaluation of asymmetrical monocarbonyl analogs of curcumin as anti-inflammatory agents
Yali Zhang,1,2,* Chengguang Zhao,1,2,* Wenfei He,2,* Zhe Wang,2 Qilu Fang,2 Bing Xiao,2 Zhiguo Liu,2 Guang Liang,2 Shulin Yang1 1School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing, Jiangsu, People's Republic of China; 2Chemical Biology R...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2014-04-01
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| Series: | Drug Design, Development and Therapy |
| Online Access: | http://www.dovepress.com/discovery-and-evaluation-of-asymmetrical-monocarbonyl-analogs-of-curcu-peer-reviewed-article-DDDT |
| _version_ | 1818001789350313984 |
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| author | Zhang Y Zhao C He W Wang Z Fang Q Xiao B Liu Z Liang G Yang S |
| author_facet | Zhang Y Zhao C He W Wang Z Fang Q Xiao B Liu Z Liang G Yang S |
| author_sort | Zhang Y |
| collection | DOAJ |
| description | Yali Zhang,1,2,* Chengguang Zhao,1,2,* Wenfei He,2,* Zhe Wang,2 Qilu Fang,2 Bing Xiao,2 Zhiguo Liu,2 Guang Liang,2 Shulin Yang1 1School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing, Jiangsu, People's Republic of China; 2Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, University Town, Wenzhou, Zhejiang, People's Republic of China *These authors contributed equally to this work 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. Keywords: sepsis, inflammatory cytokines, anti-inflammation, quantitative structure–activity relationship |
| first_indexed | 2024-04-14T03:38:53Z |
| format | Article |
| id | doaj.art-a76222826cf84e3493013974d1741340 |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-04-14T03:38:53Z |
| publishDate | 2014-04-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-a76222826cf84e3493013974d17413402022-12-22T02:14:39ZengDove Medical PressDrug Design, Development and Therapy1177-88812014-04-012014default37338216356Discovery and evaluation of asymmetrical monocarbonyl analogs of curcumin as anti-inflammatory agentsZhang YZhao CHe WWang ZFang QXiao BLiu ZLiang GYang SYali Zhang,1,2,* Chengguang Zhao,1,2,* Wenfei He,2,* Zhe Wang,2 Qilu Fang,2 Bing Xiao,2 Zhiguo Liu,2 Guang Liang,2 Shulin Yang1 1School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing, Jiangsu, People's Republic of China; 2Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, University Town, Wenzhou, Zhejiang, People's Republic of China *These authors contributed equally to this work 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. Keywords: sepsis, inflammatory cytokines, anti-inflammation, quantitative structure–activity relationshiphttp://www.dovepress.com/discovery-and-evaluation-of-asymmetrical-monocarbonyl-analogs-of-curcu-peer-reviewed-article-DDDT |
| spellingShingle | Zhang Y Zhao C He W Wang Z Fang Q Xiao B Liu Z Liang G Yang S Discovery and evaluation of asymmetrical monocarbonyl analogs of curcumin as anti-inflammatory agents Drug Design, Development and Therapy |
| title | Discovery and evaluation of asymmetrical monocarbonyl analogs of curcumin as anti-inflammatory agents |
| title_full | Discovery and evaluation of asymmetrical monocarbonyl analogs of curcumin as anti-inflammatory agents |
| title_fullStr | Discovery and evaluation of asymmetrical monocarbonyl analogs of curcumin as anti-inflammatory agents |
| title_full_unstemmed | Discovery and evaluation of asymmetrical monocarbonyl analogs of curcumin as anti-inflammatory agents |
| title_short | Discovery and evaluation of asymmetrical monocarbonyl analogs of curcumin as anti-inflammatory agents |
| title_sort | discovery and evaluation of asymmetrical monocarbonyl analogs of curcumin as anti inflammatory agents |
| url | http://www.dovepress.com/discovery-and-evaluation-of-asymmetrical-monocarbonyl-analogs-of-curcu-peer-reviewed-article-DDDT |
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