7,8-Dihydroxy-3-(4-nitrophenyl)coumarin induces cell death via reactive oxygen species-independent S-phase cell arrest.

We herein report the synthesis and in vitro cytotoxicity of 3-arylcoumarin derivatives (6a-f and 7a-f) in human liver (HepG2), prostate (LNCap), and pancreatic (BxPC3) cancer cell lines. Among the tested compounds, 7,8-dihydroxy-3-(4-nitrophenyl) coumarin (7b) showed the highest cytotoxicity in the HepG2 cell line. The mechanism of cytotoxic action indicated that compound (7b) arrested HepG2 cells at the S phase of the cell cycle progression, induced loss of mitochondrial membrane potential, and caused reactive oxygen species (ROS)-independent cell death. The cell viability result of pretreated HepG2 cells with antioxidant N-acetylcysteine followed by compound (7b) treatment and the free radical scavenging activities of compound (7b) confirmed the ROS-independent cell death. These results demonstrate that compound (7b) could serve as a valuable template for the development of novel synthetic compounds as potential anticancer agents for hepatocellular carcinoma treatment.