Synthesis and evaluation of cytotoxicity of 6-amino-4-aryl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitriles

Several derivatives of 6-amino-4-aryl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitriles were synthesized via Biginelli type reaction and tested for their anti-proliferative activity on human breast cancer (MCF-7) and human colon carcinoma (HT29) cell lines. Malignant and non-malignant cells were cultivated in RPMI medium and incubated with different concentrations of these pyrimidines. Cell viability was evaluated by MTT assay. Apoptotic cells were determined using DAPI (4'-6-diamidino-2-phenylindole) and propidium iodide staining of DNA fragmentation by flow cytometry (sub-G1 peak). 6-Amino-4-(4-chlorophenyl)-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile and 6-amino-4-[4-dimethylamino)phenyl]-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile decreased the viability of MCF-7 and HT29 cells, in contrast to L929 cells. These compounds induced a sub-G1 peak inflow cytometry histograms of treated cells indicating that apoptosis is involved in their toxicity.