Role of cell cycle events and apoptosis in mediating the anti-cancer activity of a silver(I) complex of 4-hydroxy-3-nitro-coumarin-bis(phenanthroline) in human malignant cancer cells.

The central objective of the current study was to investigate the potential in vitro anti-proliferative effect of 4-hydroxy-3-nitro-coumarin (hncH), and the mixed-ligand silver (I) complex of 4-oxy-3-nitro-coumarin-bis(phenanthroline), [Ag(hnc)(phen)(2)] using four human-derived model cell lines. In addition, selected mechanistic studies were carried out using the most sensitive of the four cell lines. Results obtained show that the complex could decrease the proliferation of all four cell lines including neoplastic renal and hepatic, namely A-498 and HepG(2) cells, respectively, along with two non-neoplastic renal and hepatic cell lines, HK-2 and Chang, respectively.

Apoptotic cell death: a possible key event in mediating the in vitro anti-proliferative effect of a novel copper(II) complex, [Cu(4-Mecdoa)(phen)(2)] (phen=phenanthroline, 4-Mecdoa=4-methylcoumarin-6,7-dioxactetate), in human malignant cancer cells.

The central objective of the current study was to investigate the potential in vitro anti-proliferative effect of the parent ligand, 4-methylcoumarin-6,7-dioxyacyeic acid (4-MecdoaH(2)), and its copper (II) complex, bis(phenanthroline4-methylcoumarin-6,7-dioxacetatocopper(II) ([Cu(4-Mecdoa)(phen)(2)]) using four human model cell lines. In addition, selected mechanistic studies were carried out using the most sensitive of the four cell lines. Results obtained show that the complex could alter proliferation of both human neoplastic renal (A-498) and hepatic (HepG2) cells.

An in vitro investigation of the induction of apoptosis and modulation of cell cycle events in human cancer cells by bisphenanthroline-coumarin-6,7-dioxacetatocopper(II) complex.

The central objective of the current study was to investigate the potential in vitro anti-proliferative properties of the parent ligand, coumarin-dioxy-acetic acid (cdoaH(2)), and its copper complex, copper-coumarin-dioxyacetic acetate-phenathroline ([Cu(cdoa)(phen)(2)]) using four human-derived model cell lines, two neoplastic and two non-neoplastic. In addition, selected mechanistic studies were carried out using one of the neoplastic-derived model cell lines, Hep-G2. Results obtained show that the complex, rather than the ligand, could alter the proliferation of both human neoplastic renal (A-498) and hepatic (Hep-G2) cells.

Mechanism of action of coumarin and silver(I)-coumarin complexes against the pathogenic yeast Candida albicans.

The anti-fungal activity and mode of action of a range of silver(I)-coumarin complexes was examined. The most potent silver(I)-coumarin complexes, namely 7-hydroxycoumarin-3-carboxylatosilver(I), 6-hydroxycoumarin-3-carboxylatosilver(I) and 4-oxy-3-nitrocoumarinbis(1,10-phenanthroline)silver(I), had MIC80 values of between 69.1 and 4.

A study of the role of apoptotic cell death and cell cycle events mediating the mechanism of action of 6-hydroxycoumarin-3-carboxylatosilver in human malignant hepatic cells.

Previously our research group has studied the anti-proliferative effects of a series of hydroxylated derivatives and silver (I) complexes of coumarin-3-carboxylic acid (C-3-COOH) using two human-derived carcinoma cell lines (A-498 and Hep-G2). Results obtained suggested that both hydroxylation and complexation with silver served to significantly augment the cytotoxic properties of C-3-COOH, to yield a compound, namely 6-hydroxycoumarin-3-carboxylatosilver (6-OH-C-COO-Ag) which could act as a potent and cyto-selective agent, capable of killing cancer cells, and with limited toxicity to cells derived from normal tissue. Here we seek to expand on these findings by probing the molecular mechanism underlying this effect.

In vitro anti-tumour and cyto-selective effects of coumarin-3-carboxylic acid and three of its hydroxylated derivatives, along with their silver-based complexes, using human epithelial carcinoma cell lines.

The chemotherapeutic potential of coumarin-3-carboxylic acid (C-3-COOH) and a series of three hydroxylated coumarin-3-carboxylic acid ligands, namely 6-hydroxy-coumarin-3-carboxylic acid (6-OH-C-3-COOH), 7-hydroxy-coumarin-3-carboxylic acid (7-OH-C-3-COOH) and 8-hydroxy-coumarin-3-carboxylic acid (8-OH-C-3-COOH), along with their corresponding silver-based complexes, namely 6-hydroxycoumarin-3-carboxylatosilver (6-OH-C-COO-Ag), 7-hydroxycoumarin-3-carboxylatosilver (7-OH-C-COO-Ag) and 8-hydroxycoumarin-3-carboxylatosilver (8-OH-C-COO-Ag), was determined using two human-derived carcinoma (A-498 and Hep-G2), along with two non-carcinoma human-derived cell lines (CHANG and HK-2). All of the ligands and their silver complexes induced a concentration-dependent cytotoxic effect. Furthermore, hydroxylation of C-3-COOH and its subsequent complexation with silver led to the production of a series of compounds with dramatically enhanced cytotoxicity, with 6-OH-C-3-COO-Ag having the greatest activity.