title: Discovery and evaluation of piperid-4-one-containing mono-carbonyl analogs of curcumin as anti-inflammatory agents.
abstract: We previously reported the design and discovery of three series of 5-carbon linker-containing mono-carbonyl analogs of curcumin (MCACs) as excellent anti-inflammatory agents. In continuation of our ongoing research, we designed and synthesized the fourth series of MCACs, whose central linker is a piperid-4-one. Their inhibitory effects against IL-6 production were evaluated in lipopolysaccharide (LPS)-stimulated macrophages. Among them, compounds F8, F29, F33, F35, and F36 exhibited the IC50 values under 5 μM. The structure-activity relationship was discussed. Mechanistically, F35 and F36 dose-dependently prevented LPS-induced NF-κB and ERK activation. Finally, pretreatment with F35 and F36 significantly protected the C57B/L6 mice from LPS-induced septic death. Together, these data present a series of new analogs of curcumin as promising anti-inflammatory agents.
authors.affiliation: School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing, Jiangsu 210094, China.
authors.forename: Jianzhang
authors.initials: J
authors.lastname: Wu
authors.forename: Yali
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yuepiao
authors.initials: Y
authors.lastname: Cai
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Bixia
authors.initials: B
authors.lastname: Weng
authors.forename: Qinqin
authors.initials: Q
authors.lastname: Tang
authors.forename: Xiangjian
authors.initials: X
authors.lastname: Chen
authors.forename: Zheer
authors.initials: Z
authors.lastname: Pan
authors.forename: Guang
authors.initials: G
authors.lastname: Liang
authors.forename: Shulin
authors.initials: S
authors.lastname: Yang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D003474:Curcumin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D007249:Inflammation; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D010881:Piperidones / Q000138:chemical synthesis* / Q000494:pharmacology; D018805:Sepsis / Q000139:chemically induced / Q000378:metabolism / Q000401:mortality / Q000517:prevention & control*; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D016019:Survival Analysis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010881:Piperidones; D048049:Extracellular Signal-Regulated MAP Kinases; D003474:Curcumin