الفهرس 
review of literatureOnly 14 pages are availabe for public view
 |  | from | 185 |  |  |
| | | from | 185 | | |
Abstract
Cancer is a group of many related diseases. All forms of cancer involve out-of-control growth and spread of abnormal cells. Normal body cells grow, divide, and die in an orderly fashion. Cancer cells, however, continue to grow, divide and can spread to other parts of the body. These cells accumulate and form tumors that may compress, invade, and destroy normal tissue.
In this study Potassium salt of 2-thioxo-4-hydroxycoumarin [3, 4-b] pyrimidine (3a) and 9-bromo-2-thioxo-4-hydroxycoumarin [3, 4-b] pyrimidine(3b) (coumarin fused with pyrimidine ring) were synthesized and evaluating for their in vitro and in vivo anticancer activities. The prepared compounds have been also evaluated for antioxidant activity and its ability to induce apoptosis.
Materials have been used:
-Synthetic compounds (3a, 3b)
-Human tumor cell lines (MCF-7, HepG2, HCT116. PC3)
-Ehrlish ascites carcinoma cells
-Experimental animal (Swiss female albino mice)
Results:
In vitro study
The compounds (3a, 3b) exhibited a significant anticancer activity towards breast adenocarcinoma (MCF-7), hepatocellular carcinoma (HepG2), colon cancer (HCT116) and prostate cancer (PC3 cancer) cell lines at doses 25, 5, 25, 25 µg/mL respectively for compound 3a and 50 µg/mL for compound 3b for all cell lines.
Also, in vivo study of, (3a, 3b) compounds revealed a significant anticancer activity towards Ehrlich ascites carcinoma (EAC) cells by reduction of its volume to 55.5% and 73.3% (p<0.001), in the treated groups; respectively. And significantly decrease in the cell count by 65.9% and 78.9%, in treated groups (p<0.001); respectively, compared to the positive control group.
Compound (3a, 3b) treated groups showed a significant decrease in MDA and NO concentration in EAC and in plasma samples compared to the positive control group. While, CAT and SOD activities showed a significantly increase in EAC and plasma samples in (3b, 3b) treated group, compared to positive control.
Compounds (3a, 3b) showed a significantly increase in Caspase-3 activity by 85.9% and 269.23%, respectively; compared to the positive control group. Also, the treatments with 3a and 3b (5 mg/kg, and 7.5 mg/kg, I.P.) showed a significantly increase in cytochrome c by 85.9% and 269.23%, respectively; compared to the positive control group.
It turned out that they reduced cell viability of cancer cells in a time and concentration dependent manner in vitro and in vivo studies. The synthesized compounds have potent antioxidant activity and good inducer for apoptosis by induction of caspase-3 and releasing of cytochrome c. as the anti-tumor and antioxidant effects of compound 3b more than compound 3a due to Br-substitution on coumarin ring.