title: Anti-inflammatory properties of an isoxazole derivative - MZO-2.
abstract: BACKGROUND
  A series of new isoxazole derivatives of expected immunosuppressive activities was synthesized. Following in vitro screening in the human cell models, the activity of MZO-2 compound (ethyl N-{4-[(2,4-dimethoxybenzyl)carbamoyl]-3-methylisoxazol-5-yl}acetimidate) in mouse in vivo models was evaluated.
  
  
  METHODS
  In vitro tests included evaluation of: peripheral blood mononuclear cells (PBMC) viability, phytohemagglutinin (PHA)-induced PBMC proliferation and lipopolysaccharide (LPS)-induced tumor necrosis factor α (TNF α) production in whole blood cell cultures. MZO-2 was studied in mice for its effects on: humoral immune response to sheep erythrocytes (SRBC), delayed type hypersensitivity (DTH) to ovalbumin (OVA), contact sensitivity to oxazolone and carrageenan-induced foot pad edema. In addition, the effect of MZO-2 on expression of caspases in Jurkat cells was determined.
  
  
  RESULTS
  The studied compounds exhibited differential, dose-dependent effects to suppress PHA-induced PBMC proliferation and a weak property to suppress LPS-induced production of TNF α. MZO-2 had no effect on the induction phase of the humoral immune response to SRBC in vitro and in vivo, but moderately suppressed the induction phase of DTH to OVA. Its inhibitory effect on carrageenan-induced paw inflammation was potent. Likewise, MZO-2, applied in ointment, was very effective in reducing ear edema and number of lymphocytes in draining lymph nodes of mice sensitized to oxazolone, comparably to tacrolimus, the reference drug. The expression of caspases 3, 8 and 9 in Jurkat cells was inhibited by the compound.
  
  
  CONCLUSIONS
  MZO-2, applied systemically or locally, may serve as a potential drug for amelioration of inflammatory processes.
authors.affiliation: Department of Organic Chemistry, Faculty of Pharmacy, Wrocław Medical University, Wrocław, Poland. Electronic address: marcin.maczynski@umed.wroc.pl.
authors.forename: Marcin
authors.initials: M
authors.lastname: Mączyński
authors.affiliation: Laboratory of Immunobiology, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Artym
authors.affiliation: Laboratory of Immunobiology, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
authors.forename: Maja
authors.initials: M
authors.lastname: Kocięba
authors.affiliation: Laboratory of Immunobiology, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Kochanowska
authors.affiliation: Department of Organic Chemistry, Faculty of Pharmacy, Wrocław Medical University, Wrocław, Poland.
authors.forename: Stanisław
authors.initials: S
authors.lastname: Ryng
authors.affiliation: Laboratory of Immunobiology, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Zimecki
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002351:Carrageenan / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D056724:Immunity, Humoral / Q000187:drug effects / Q000276:immunology; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D007555:Isoxazoles / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D010047:Ovalbumin / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D012756:Sheep; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D007555:Isoxazoles; D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D014409:Tumor Necrosis Factor-alpha; D002351:Carrageenan; D010047:Ovalbumin
keywords: Carrageenan; Caspases; Contact sensitivity; Isoxazoles; Suppression; Tacrolimus