title: Synthesis and selected immunological properties of substituted quino[3,2-b]benzo[1,4]thiazines.
abstract: A new type of azaphenothiazines - tetracyclic quino[3,2-b]benzo[1,4]thiazines, possessing common substituents (H, CH3, Cl, Br, F, CF3, SCH3) in positions 8-10 and pharmacophoric aminoalkyl substituents in position 6, were obtained from diquinodithiin and 2,2'-dichloro-3,3'-diquinolinyl disulfide in several-step syntheses. Sixty one compounds, grouped as the 6H, 6-dialkylaminoalkyl, 6-acylaminoalkyl and sulfonylaminoalkyl derivatives, were tested for cytotoxicity, their effects on phytohemagglutin A (PHA)-induced proliferative response of human peripheral blood mononuclear cells (PBMC) and lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-α) production by these cells. The compounds exhibited differential inhibitory activities in these tests and significantly varied in terms of cytotoxicity. The most promising compounds were tested for growth inhibition of leukemia L-1210 cells, colon cancer SV-948 cells and epidermal carcinoma A-341 cells. The most active compounds exhibited anticancer activity against these cell lines comparable to that of cisplatin. The structure-activity relationship of the compounds were discussed.
authors.affiliation: The Medical University of Silesia, Department of Organic Chemistry, Jagiellońska 4, 41-200 Sosnowiec, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Jeleń
authors.forename: Krystian
authors.initials: K
authors.lastname: Pluta
authors.forename: Michał
authors.initials: M
authors.lastname: Zimecki
authors.forename: Beata
authors.initials: B
authors.lastname: Morak-Młodawska
authors.forename: Jolanta
authors.initials: J
authors.lastname: Artym
authors.forename: Maja
authors.initials: M
authors.lastname: Kocięba
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008956:Models, Chemical; D015394:Molecular Structure; D010835:Phytohemagglutinins / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013843:Thiazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D013843:Thiazines; D014409:Tumor Necrosis Factor-alpha