title: Synthesis and biological evaluation of allylated and prenylated mono-carbonyl analogs of curcumin as anti-inflammatory agents.
abstract: Curcumin has been shown to possess anti-inflammatory activities but has been limited for its low stability and poor bioavailability. We have previously reported four series of 5-carbon linker-containing mono-carbonyl analogs of curcumin (MACs). In continuation of our ongoing research, we designed and synthesized 33 novel allylated or prenylated MACs here, and evaluated their anti-inflammatory effects in RAW 264.7 macrophages. A majority of them effectively inhibited the LPS-induced expression of TNF-α and IL-6, especially IL-6. The preliminary SAR and quantitative SAR analysis were conducted. Compound 14q is the most potent analog among them, and exhibits significant protection against LPS-induced death in septic mice. Together, these data present a series of new analogs of curcumin as promising anti-inflammatory agents.
authors: Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang 325035, China; Wenzhou Undersun Biotechnology Co., Ltd., Wenzhou, Zhejiang, China.
authors: Zhiguo
authors: Z
authors: Liu
authors: Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang 325035, China.
authors: Longguang
authors: L
authors: Tang
authors: School of Environmental and Biological Engineering, Nanjing University of Science and Technology, No. 200 Xiaolingwei Road, Xuanwu District, Nanjing, Jiangsu 210094, China.
authors: Peng
authors: P
authors: Zou
authors: School of Environmental and Biological Engineering, Nanjing University of Science and Technology, No. 200 Xiaolingwei Road, Xuanwu District, Nanjing, Jiangsu 210094, China.
authors: Yali
authors: Y
authors: Zhang
authors: Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang 325035, China.
authors: Zhe
authors: Z
authors: Wang
authors: Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang 325035, China.
authors: Qilu
authors: Q
authors: Fang
authors: Department of Pediatrics, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors: Lili
authors: L
authors: Jiang
authors: Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang 325035, China.
authors: Gaozhi
authors: G
authors: Chen
authors: Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang 325035, China.
authors: Zheng
authors: Z
authors: Xu
authors: Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang 325035, China. Electronic address: zhj@wzmc.net.
authors: Huajie
authors: H
authors: Zhang
authors: Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang 325035, China. Electronic address: cuiliang1234@163.com.
authors: Guang
authors: G
authors: Liang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D001483:Base Sequence; D001682:Biological Availability; D002460:Cell Line; D003474:Curcumin / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D017931:DNA Primers; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008810:Mice, Inbred C57BL; D054876:Prenylation; D060888:Real-Time Polymerase Chain Reaction; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship
chemical_list: D000893:Anti-Inflammatory Agents; D017931:DNA Primers; D003474:Curcumin
keywords: Anti-inflammation; Curcumin; IL-6; Mono-carbonyl analogs; QSAR; TNF-α