Potassium salt of 2–thioxo–4–hydroxycoumarin [3, 4–b]  pyrimidine and 9–bromo–2–thioxo–4–hydroxycoumarin  [3, 4–b] pyrimidine inhibits tumor growth in vitr

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

Volume : III, Issue : VI, June - 2013

Potassium salt of 2–thioxo–4–hydroxycoumarin [3, 4–b] pyrimidine and 9–bromo–2–thioxo–4–hydroxycoumarin [3, 4–b] pyrimidine inhibits tumor growth in vitr

Faten Zahran, I. M. El Deen, M. M. El Behary, Akaber T. Keshta

Abstract :

Coumarin and their derivatives are important and useful compounds with diverse pharmacological properties. In the present study, we evaluated the in vitro cytotoxic activity of new Coumarin derivatives: Potassium salt of 2–thioxo–4–hydroxycoumarin [3, 4–b] pyrimidine and 9–omo–2–thioxo–4–hydroxycoumarin [3, 4–b] pyrimidine against MCF–7 (human east cancer), HePG2 (Hepatocellular carcinoma), HCT116 (human colon cancer), PC3 (human prostate cancer). In order to find new drugs with anticancer activities prepared compounds were evaluated for their in vitro and in vivo anticancer activities. Coumarino[3, 4–b] pyrimidine –2–thioles (4a,b) were prepared via cyclocondensation of 6–substituted–3–ethoxycarbonylcoumarin (2a, b) with thiourea in the presence of anhydrous potassium carbonate to give the potassium salt of Coumarino[3, 4–b] pyrimidine –2–thioles (3a, b), followed by acidification of (3a, b), with 2 N hydrochloric acid . The compounds [3a & 3b] exhibited a significant anticancer activity towards MCF–7, HEPG2, HCT116 and PC3 cancer 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. It turned out that they reduced cell viability of cancer cells in a time and concentration dependent manner in vitro and in vivo studies.