Cytotoxic Activity of New Acetoxycoumarin Derivatives in Cancer Cell Lines

Abstract

Background: 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 acetoxycoumarin  derivatives: 4-(7-methoxy-4-methyl-2-oxo-2H-chromen-3-yl)phenyl acetate (1),  4-(1-methyl-3-oxo-3H-benzo[f]chromen-2-yl)phenyl acetate (2), 4-(6- propionamido-4-methyl-2-oxo-2H-chromen-3-yl) phenyl acetate (3), 4-(7- acetoxy-2-oxo-4-phenyl-2H-chromen-3-yl)phenyl acetate (4), 4-(2-oxo-4- phenyl-2H-chromen-3-yl)phenyl acetate (5), 4-(6-bromo-2-oxo-4-phenyl-2H- chromen-3-yl)phenyl acetate (6), 4-(7-(diethylamino)-4-methyl-2-oxo-2H- chromen-3-yl)phenyl acetate (7), 4-(6,8-dibromo-4-methyl-2-oxo-2H-chromen-3 -yl)phenyl acetate (8) against A549 human lung cancer, CRL 1548 rat liver cancer and CRL 1439 normal rat liver cells. Materials and Methods: The  cytotoxic activity was evaluated by crystal violet dye-binding assay. The  effect of compounds 5 and 7 on different phases of the cell cycle was  determined using flow cytometry. Results: In the A549 lung cancer cell line, the 50% lethal dose (LD50) values for compounds 1-4, 6 and 8 were found to be >100 μM while those for 5 and 7 were 89.3 and 48.1 μM, respectively after 48 h treatment. In the CRL 1548 liver cancer cell line, only compound 7 showed toxicity, with an LD50 of 45.1 μM. Compounds 5 and 7 caused different cell phase arrest in lung and liver cancer cell lines. Conclusion: The results indicate that 4-(7-(diethylamino)-4-methyl-2-oxo-2H-chromen-3-yl) phenyl acetate (7) had the highest cytotoxic activity in all of the examined  cell lines.