MODE OF ACTION OF POTASSIUM SALT OF 2-THIOXO-4-HYDROXYCOUMARIN [3, 4-B] PYRIMIDINE AND 9-BROMO-2-THIOXO-HYDROXYCOUMARIN [3, 4-B] PYRIMIDINE AGAINST EHRLICH ASCITES CARCINOMA CELLS

Faten Zahran, Akaber T. Keshta, I. M. EL-Deen, M. M. El-behary

Abstract: Coumarin and pyrimidine derivatives have attracted intense interest in recent years because they have anti-tumor, antioxidant activities, and induce apoptosis. Our study aims to evaluate the antitumor and anti-oxidant activities of new Coumarin derivatives: Potassium salt of 2-thioxo-4-hydroxycoumarin [3, 4-b] pyrimidine and 9-bromo-2-thioxo-hydroxycoumarin [3, 4-b] pyrimidine against in vivo tumor model. Coumarino [3, 4-b] pyrimidine -2-thioles (4 a,b) were prepared and their cytotoxicity were determined. The compounds [3a & 3b] exhibited a significant anti-oxidant activity towards Ehrlich ascites carcinoma (EAC) cells by reduction the MDA by 30.3% & 54.9% and NO concentration by 19.4% & 39.6% (p<0.001), respectively; compared to the positive control group. Whereas significantly increase in the CAT activity by 150%, 700%, respectively; and SOD activity by 102.9% and 379.9%, (p<0.001) respectively; in [3a & 3b] treated groups compared to the positive control group. Anticancer agent kills tumors at least partially through induction of apoptosis. Furthermore, the treatments with 3a and 3b showed a significantly increase in  Caspase-3 activity by 85.9% and 269.23%, (p<0.001), respectively; and cytochrome c by 85.9% and 269.23%, (p<0.001), respectively; compared positive control group. The synthesized compounds have potent antioxidant activity and good inducer for apoptosis by induction of caspase-3 and releasing of cytochrome c.

Keywords: Coumarins, Pyrimidine, Ehrlich ascites carcinoma cells, apoptosis.

Pages: 76 – 89 | Full PDF Paper