SYNTHESIS AND EVALUATION OF CYTOTOXICITY OF 6-AMINO-4-ARYL-2-THIOXO-1,2,3,4-TETRAHYDROPYRIMIDINE-5-CARBONITRILES

^#E-mail: mbakavoli@um.ac.ir; mbakavoli@yahoo.com

*Chemistry Department, Payame Noor University, 19395-4697 Tehran, I. R. Iran;
**Department of Clinical Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran;
***Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, 91775-1436 Iran

Received June 05, 2015; in final form August 10, 2015

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.

Keywords: apoptosis, cytotoxic evaluation, pyrimidines, toxicity.

Биоорг. химия 2016, 42 (3): 351-357