We evaluated the potential activity of novel N-1-sulfonyl derivatives of
pyrimidine bases
uracil and
cytosine on
pancreatic carcinoma cells (MIAPaCa2), colon
carcinomas cells (HT-29, CaCo2), cervical
carcinoma cells (HeLa) and poorly-differentiated cells from
lymph node metastasis of colon
carcinoma (SW-620). The cytotoxicity of
N-1-sulfonylpyrimidine derivatives was analyzed with the MTT cell survival assay and their antiproliferative activity was measured via radioactive precursors incorporation assay. The
N-1-sulfonylpyrimidine derivatives affected the growth of all examined cell lines at concentrations of 10(-8)-10(-5) M, by 25-70%. Growth inhibition depended on the tumor cell line type and the concentration of investigated compounds. The compounds 2, 4, 7, 8 and 9 inhibited
DNA,
RNA and
protein synthesis in CaCo2, MIAPaCa2 and HeLa cells. The exposure of
tumor cells in vitro to compounds 2, 4, 7, 8, 9, 10 and 11, at the 10(-6) M concentration, caused both morphological (condensation of
chromatin, cell shrinkage), as well as biochemical changes (ladder pattern of DNA fragmentation and exposure of
phosphatidylserine on outer
lipid bilayer plasma membrane) characteristic of apoptosis. After 24 hours of the
N-1-sulfonylpyrimidine derivative application, the p53
oncoprotein expression could not be detected by immunocytochemical analysis. On the basis of present results it can be concluded that novel
N-1-sulfonylpyrimidine derivatives are promising
antitumor agents with a strong antiproliferative activity and an ability to induce apoptosis in treated
tumor cells.