title: Synthesis and optimization of novel allylated mono-carbonyl analogs of curcumin (MACs) act as potent anti-inflammatory agents against LPS-induced acute lung injury (ALI) in rats.
abstract: A series of novel symmetric and asymmetric allylated mono-carbonyl analogs of curcumin (MACs) were synthesized using an appropriate synthetic route and evaluated experimentally thru the LPS-induced expression of TNF-α and IL-6. Most of the obtained compounds exhibited improved water solubility as a hydrochloride salt compared to lead molecule 8f. The most active compound 7a was effective in reducing the Wet/Dry ratio in the lungs and protein concentration in bronchoalveolar lavage fluid. Meanwhile, 7a also inhibited mRNA expression of several inflammatory cytokines, including TNF-α, IL-6, IL-1β, and VCAM-1, in Beas-2B cells after Lipopolysaccharide (LPS) challenge. These results suggest that 7a could be therapeutically beneficial for use as an anti-inflammatory agent in the clinical treatment of acute lung injury (ALI).
authors.affiliation: Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang, 325035, China.
authors.forename: Heping
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang, 325035, China; The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
authors.forename: Tingting
authors.initials: T
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: Chenyu
authors.initials: C
authors.lastname: Qiu
authors.affiliation: Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang, 325035, China; The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
authors.forename: Beibei
authors.initials: B
authors.lastname: Wu
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: Lingfeng
authors.initials: L
authors.lastname: Chen
authors.affiliation: Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang, 325035, China.
authors.forename: Qinqin
authors.initials: Q
authors.lastname: Xia
authors.affiliation: Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang, 325035, China.
authors.forename: Chenglong
authors.initials: C
authors.lastname: Li
authors.affiliation: The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China. Electronic address: pzhoubin@sina.com.
authors.forename: Bin
authors.initials: B
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: lzgcnu@163.com.
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: Guang
authors.initials: G
authors.lastname: Liang
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000235:genetics; D008070:Lipopolysaccharides; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats; D012995:Solubility; D017155:Wettability
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D003474:Curcumin
keywords: Acute lung injury; Chemical stability; Drug design; Mono-carbonyl analogs of curcumin; Water solubility