This study determined the cytotoxic, cyto-selective and mutagenic potential of novel
quinolinone Schiff base ligands and their corresponding
copper(II) complexes in human-derived hepatic
carcinoma cells (Hep-G2) and non-malignant human-derived hepatic cells (Chang). Results indicated that complexation of
quinolinone Schiff bases with
copper served to significantly enhance cytotoxicity. Here, the complex of (7E)-7-(3-ethoxy-2-hydroxybenzylideamino)-4-methylquinolin-2(1H)-one (TV117-FM) exhibited the lowest IC(50) value (17.9 μM) following 96 h continuous exposure, which was comparable to
cisplatin (15.0 μM). However, results revealed that TV117-FM lacked cytoselectivity over non-malignant cells. Additionally, the complex was minimally effluxed from cells via Pglycoprotein (P-gp) and was shown to be non-mutagenic in the Standard Ames test. Furthermore,
BrdU incorporation assays showed that it was capable of inhibiting
DNA synthesis in a concentrationand time-dependent manner. However, inhibition was not as a consequence of
DNA intercalation, as illustrated in electrophoretic mobility shift assays. Interestingly, it was shown that the
ligand was capable of inhibiting the action of
topoisomerase II, but this was lost following complexation. This indicated that the mechanism of action of the novel
copper(II) complex was different from that of the parent
ligand and suggests that TV117-FM may have a therapeutic role to play in the treatment of
hepatocellular carcinoma. Studies are currently underway to elucidate the exact in vitro mechanism of action of this novel,
metal-based anti-
cancer agent.