title: Immunological activity of new heterocyclic amides of 5-amino-3-methylisoxazole-4-carboxylic acid.
abstract: In the present study, some new amides of 5-amino-3-methylisoxazole-4-carboxylic acid were obtained. All new structures possessed markedly different groups of electron acceptor character, different spatial structure and they contained nitrogen heteroatom, enabling formation of salts and, at the same time, higher biological availability. They were examined for immunomodulating activity in comparison with cyclosporine A (CsA). We investigated effects of the compounds on the lipopolysaccharide (LPS)-induced production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) by human peripheral blood cells. Some compounds exhibited suppressory action which corresponded with increasing electronoacceptor nature of the amide substituent. Two compounds, characterized by flat aromatic rings, demonstrated quite different properties. Much higher activity was expressed by compounds which contained -NH group, the group which conditioned immunostimulatory activity in other compounds described previously.
authors.affiliation: Wrocław Medical University, Faculty of Pharmacy, Department of Organic Chemistry, Poland.
authors.forename: S
authors.initials: S
authors.lastname: Ryng
authors.forename: M
authors.initials: M
authors.lastname: Zimecki
authors.forename: A
authors.initials: A
authors.lastname: Fedorowicz
authors.forename: A
authors.initials: A
authors.lastname: Koll
mesh_terms: D000276:Adjuvants, Immunologic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis; D007555:Isoxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000276:Adjuvants, Immunologic; D002264:Carboxylic Acids; D007166:Immunosuppressive Agents; D015850:Interleukin-6; D007555:Isoxazoles; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016572:Cyclosporine