title: Synthesis and Evaluation of Anti-inflammatory N-Substituted 3,5-Bis(2-(trifluoromethyl)benzylidene)piperidin-4-ones.
abstract: A total of 24 N-substituted 3,5-bis(2-(trifluoromethyl)benzylidene)piperidin-4-one derivatives were synthesized via aldol condensation, and their anti-inflammatory activities were evaluated. These compounds were found to have no significant cytotoxicity against mouse bone marrow cells in vitro. However, some compounds, such as c6 (N-(3-methylbenzoyl)-3,5-bis-(2-(trifluoromethyl)benzylidene)piperidin-4-one) and c10 (N-(2-chlorobenzoyl)-3,5-bis-(2-(trifluoromethyl)benzylidene)piperidin-4-one), displayed potent anti-inflammatory activity by inhibiting lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), IL-1β, prostaglandin E2 (PGE2), and nitric oxide (NO) production in RAW 264.7 cells. Treatment with c6 or c10 at 2.5 or 10 mg kg-1significantly decreased the paw edema induced by carrageenan in rats, and the anti-inflammatory effects of these compounds were found to be better than those of celecoxib or indomethacin as well as their parent compound C66 (2,6-bis-(2-(trifluoromethyl)benzylidene)cyclohexanone). Pharmacokinetic analysis indicated that c6 has better bioavailability than curcumin. Therefore, these compounds may be valuable leads for the development of new anti-inflammatory drugs.
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Chashan Campus Chashan University Town, Wenzhou, 325035, China.
authors.forename: Zixin
authors.initials: Z
authors.lastname: Xie
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Chashan Campus Chashan University Town, Wenzhou, 325035, China.
authors.forename: Zaikui
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Chashan Campus Chashan University Town, Wenzhou, 325035, China.
authors.forename: Shufang
authors.initials: S
authors.lastname: Yu
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Chashan Campus Chashan University Town, Wenzhou, 325035, China.
authors.forename: Donghua
authors.initials: D
authors.lastname: Cheng
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Chashan Campus Chashan University Town, Wenzhou, 325035, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Chashan Campus Chashan University Town, Wenzhou, 325035, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Han
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Chashan Campus Chashan University Town, Wenzhou, 325035, China.
authors.forename: Handeng
authors.initials: H
authors.lastname: Lv
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Chashan Campus Chashan University Town, Wenzhou, 325035, China.
authors.forename: Faqing
authors.initials: F
authors.lastname: Ye
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002351:Carrageenan / Q000633:toxicity; D000068579:Celecoxib / Q000494:pharmacology / Q000627:therapeutic use; D002470:Cell Survival / Q000187:drug effects; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D004797:Enzyme-Linked Immunosorbent Assay; D053583:Interleukin-1beta / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D010881:Piperidones / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D000067996:RAW 264.7 Cells; D051381:Rats; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D010881:Piperidones; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D002351:Carrageenan; D000068579:Celecoxib; D015232:Dinoprostone
keywords: anti-inflammatory activity; curcumin analogues; piperidones; synthesis