Synthesis and selected immunological properties of substituted quino[3,2-b]benzo[1,4]thiazines.
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.
T10 T11 T12 T13 T14 T15 T16 T17 T18 T19 T1 T20 T21 T2 T3 T4 T5 T6 T7 T8 T9
CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-N GENE-N CHEMICAL GENE-Y GENE-Y CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL
aminoalkyl diquinodithiin 2,2'-dichloro-3,3'-diquinolinyl disulfide tetracyclic quino[3,2-b]benzo[1,4]thiazines 6-dialkylaminoalkyl 6-acylaminoalkyl sulfonylaminoalkyl quino[3,2-b]benzo[1,4]thiazines phytohemagglutin A PHA cisplatin tumor necrosis factor alpha TNF-α H CH3 Cl Br F CF3 SCH3 azaphenothiazines