engleski

Synthesis and Biological Activity of Novel Pyrimidine Derivatives

As a part of our research program on the synthesis of novel sulfonylurea derivatives as potential anticancer agents, and reversed nucleosides as a starting material for the synthesis of optically active aliphatic and "double headed" nucleoside analogues, we synthesized 1-sulfonylpyrimidine derivatives and reversed nucleosides. The synthesis involved the condensation of silylated pyrimidine bases with aryl, heterocyclic or aliphatic sulfonyl chlorides or reaction of the pyrimidine bases with sulfonyl chlorides or activated sugar derivative in the presence of potassium carbonate, sodium hydride or triethylamine. New derivatives were tested for their antiproliferative effects using 7 different human tumor cell lines (HeLa, HEp-2, MIAPaCa2, Caco2, SW620, MCF-7, and NCI-H358) and human fibroblasts (WI38) in a parallel with 5-fluorouracil, as a standard antitumor drug. Cell lines were incubated with four 10-fold dilutions (10-8 to 10-4 M). After 72 hours of incubation, the cell growth rate was evaluated using the MTT assay. The tested compounds inhibited the growth of different tumor cell lines with varying IC50 values (>100 to 2 μ M). In comparison with 5-fluoruracil, all investigated compounds are significantly less cytotoxic on human fibroblasts.

5-Fluorouracil; N-Sulfonyl Derivatives; Reversed Nucleosides

nije evidentirano