Synthesis and selected immunological properties of 10-substituted 1,8-diazaphenothiazines.
A new type of tricyclic azaphenothiazines-1,8-diazaphenothiazines-was obtained in the reaction of 2,3- and 3,4-disubstituted pyridines. The reaction ran as the Smiles rearrangement. The 1,8-diazaphenothiazine system was determined using NOE experiment and 2D NMR spectra (COSY, HSQC, HMBC). 10H-1,8-diazaphenothiazine was transformed into 10-derivatives with alkyl, aminoalkyl, amidoalkyl, sulfonamidoalkyl, and nitrogen half-mustard groups. The compounds were tested for their effects on phytohemagglutinin A-induced proliferative response of human peripheral blood mononuclear cells (PBMC) and lipopolysaccharide-induced tumor necrosis factor alpha production by human whole blood cultures. The compounds exhibited differential, dose-dependent inhibitory activities in these tests. All the compounds were low toxic against PBMC. The compounds showing the highest antiproliferative activity strongly inhibited the growth of leukemia L-1210 and colon cancer SW-948 cell lines, similarly as cisplatin, a reference drug.
Department of Organic Chemistry, The Medical University of Silesia, Jagiellońska 4, 41-200 Sosnowiec, Poland.
Beata
B
Morak-Młodawska
Department of Organic Chemistry, The Medical University of Silesia, Jagiellońska 4, 41-200 Sosnowiec, Poland.
Krystian
K
Pluta
Department of Experimental Therapy, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, R. Weigla 12, 53-114 Wrocław, Poland.
Michał
M
Zimecki
Department of Organic Chemistry, The Medical University of Silesia, Jagiellońska 4, 41-200 Sosnowiec, Poland.
Małgorzata
M
Jeleń
Department of Experimental Therapy, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, R. Weigla 12, 53-114 Wrocław, Poland.
Jolanta
J
Artym
Department of Experimental Therapy, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, R. Weigla 12, 53-114 Wrocław, Poland.
Maja
M
Kocięba
Anticancer activity; Antiproliferative activity; Diazaphenothiazines; Phenothiazines; Thiazine ring formation