title: Design, synthesis and biological evaluation of paralleled Aza resveratrol-chalcone compounds as potential anti-inflammatory agents for the treatment of acute lung injury.
abstract: Acute lung injury (ALI) is a major cause of acute respiratory failure in critically-ill patients. It has been reported that both resveratrol and chalcone derivatives could ameliorate lung injury induced by inflammation. A series of paralleled Aza resveratrol-chalcone compounds (5a-5m, 6a-6i) were designed, synthesized and screened for anti-inflammatory activity. A majority showed potent inhibition on the IL-6 and TNF-α expression-stimulated by LPS in macrophages, of which compound 6b is the most potent analog by inhibition of LPS-induced IL-6 release in a dose-dependent manner. Moreover, 6b exhibited protection against LPS-induced acute lung injury in vivo. These results offer further insight into the use of Aza resveratrol-chalcone compounds for the treatment of inflammatory diseases, and the use of compound 6b as a lead compound for the development of anti-ALI agents.
authors.affiliation: Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang 325035, China.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Respiration, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
authors.forename: Xiangting
authors.initials: X
authors.lastname: Ge
authors.affiliation: Department of Respiration, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
authors.forename: Fengli
authors.initials: F
authors.lastname: Xu
authors.affiliation: Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang 325035, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang 325035, China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang 325035, China.
authors.forename: Jialing
authors.initials: J
authors.lastname: Pan
authors.affiliation: Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang 325035, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Respiration, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
authors.forename: Yuanrong
authors.initials: Y
authors.lastname: Dai
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang 325035, China. Electronic address: zjm@wzmc.edu.cn.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang 325035, China. Electronic address: chemime@163.com.
authors.forename: Jianpeng
authors.initials: J
authors.lastname: Feng
authors.affiliation: Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang 325035, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Liang
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000627:therapeutic use*; D001372:Aza Compounds / Q000737:chemistry / Q000627:therapeutic use*; D002460:Cell Line; D047188:Chalcones / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D000093242:Interleukin-6 Inhibitors
chemical_list: D000893:Anti-Inflammatory Agents; D001372:Aza Compounds; D047188:Chalcones; D015850:Interleukin-6; D008070:Lipopolysaccharides; D000077185:Resveratrol; D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors
keywords: Acute lung injury; Anti-inflammatory; Aza resveratrol; Chalcone; Parallel