title: Synthesis and evaluation of a series of novel asymmetrical curcumin analogs for the treatment of inflammation.
abstract: Curcumin has been reported to possess multiple bioactivities, such as antioxidant, anticancer, and anti-inflammatory properties, however the clinical application of curcumin has been significantly limited by its instability and poor metabolism. Modification of curcumin has led to discovery and development of lots of novel therapeutic candidates. In recent years acute and chronic inflammation has been the focus of numerous studies in various diseases. Here, we synthesized a series of asymmetrical curcumin analogs with high in vitro chemical stability, and their anti-inflammatory activity was evaluated in LPS-stimulated macrophages. According to the bio-screening results and QSAR analysis, these analogs exhibited potent activities against LPS-induced TNF-α and IL-6 release. Among the analogs of the potent anti-inflammatory activity, compounds 3b8 and 3b9 exhibited significant protection and possess enhanced anti-inflammatory activity thereby attenuated the LPS-induced septic death in mice.
authors.affiliation: School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing 210094, Jiangsu, China. ya-li000@163.com.
authors.forename: Yali
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy at the Affiliated Yueqing Hospital, Wenzhou Medical University, Wenzhou 325699, Zhejiang, China. leping1967@163.com.
authors.forename: Leping
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China. wujianzhang6@163.com.
authors.forename: Jianzhang
authors.initials: J
authors.lastname: Wu
authors.affiliation: Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China. jx334555768@163.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Jiang
authors.affiliation: The 2nd Affiliated Hospital, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China. luckydlily@163.com.
authors.forename: Lili
authors.initials: L
authors.lastname: Dong
authors.affiliation: The 2nd Affiliated Hospital, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China. 18368719239@163.com.
authors.forename: Fengli
authors.initials: F
authors.lastname: Xu
authors.affiliation: School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing 210094, Jiangsu, China. top_zoupeng@163.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Zou
authors.affiliation: The 2nd Affiliated Hospital, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China. yuanrongdai2000@163.com.
authors.forename: Yuanrong
authors.initials: Y
authors.lastname: Dai
authors.affiliation: The 2nd Affiliated Hospital, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China. sssxooo@sina.com.
authors.forename: Xiaoou
authors.initials: X
authors.lastname: Shan
authors.affiliation: School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing 210094, Jiangsu, China. shulin_yang@126.com.
authors.forename: Shulin
authors.initials: S
authors.lastname: Yang
authors.affiliation: Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China. wzmcliangguang@163.com.
authors.forename: Guang
authors.initials: G
authors.lastname: Liang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003474:Curcumin / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D021281:Quantitative Structure-Activity Relationship; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D003474:Curcumin