title: Synthesis and biological evaluation of piperlongumine derivatives as potent anti-inflammatory agents.
abstract: Piperlongumine (PL) and its derivatives were synthesized by the direct reaction between acid chloride of 3,4,5-trimethoxycinnamic acid and various amides/lactams. Later their anti-inflammatory effects were evaluated in lipopolysaccharide (LPS)-induced RAW-264.7 macrophages. Of the piperlogs prepared in this study, the maximum (91%) inhibitory activity was observed with PL (IC50=3 μM) but showed cytotoxicity whereas compound 3 (IC50=6 μM) which possess α,β-unsaturated γ-butyrolactam moiety offered good level (65%) of activity with no cytotoxicity. This study revealed that amide/lactam moiety connected to cinnamoyl group with minimum 3 carbon chain length and α,β-unsaturation is fruitful to show potent anti-inflammatory activity.
authors.affiliation: Department of Chemistry and Institute of Applied Chemistry, Hallym University, Chuncheon 200-702, Republic of Korea.
authors.forename: Young Hwa
authors.initials: YH
authors.lastname: Seo
authors.affiliation: Department of Biomedical Science, College of Natural Science, Catholic University of Daegu, Gyeungsan-Si 700-702, Republic of Korea.
authors.forename: Jin-Kyung
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Department of Chemistry and Institute of Applied Chemistry, Hallym University, Chuncheon 200-702, Republic of Korea. Electronic address: jgjun@hallym.ac.kr.
authors.forename: Jong-Gab
authors.initials: JG
authors.lastname: Jun
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004148:Dioxolanes / Q000737:chemistry*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D015394:Molecular Structure; D009569:Nitric Oxide / Q000378:metabolism*; D010881:Piperidones
chemical_list: D000893:Anti-Inflammatory Agents; D004148:Dioxolanes; D008070:Lipopolysaccharides; D009569:Nitric Oxide; C498077:piperlongumine; D010881:Piperidones
keywords: 3,4,5-Trimethoxycinnamic acid; Anti-inflammatory; Nitric oxide; Piperlongumine