Cytotoxic effects of selected gold(III) complexes on the murine BCL-1 B lineage leukaemia cell line

In recent years, gold(III) complexes have attracted great interest because of their cytotoxicity to cancer cells. We investigated the cytotoxic effects of three newly synthesised gold(III) complexes, [Au(en)Cl 2] + (dichloride (ethylendiamine) aurate(III)-ion), [Au(dach)Cl 2] (dichloride (1,2- diaminocyclohexane) aurate(III)-ion) and [Au(bipy)Cl 2] + (dichloride (2,2'-bipyridyl) aurate(III)-ion), on the murine BCL-1 B lineage leukaemia cell line. The cytotoxicity of these gold(III) complexes was evaluated by cytotoxic assay (MTT test). The results showed that all of the tested gold(III) complexes displayed a cytotoxic effect on BCL-1 cells. The concentration decrease was followed by a marked increase in BCL-1 cell viability. At a concentration of 125 μM, which we suppose could be used in vivo, the [Au(bipy)Cl 2] + complex showed the greatest cytotoxic effects among the tested gold(III) complexes and similar cytotoxicity asto the cisplatinum that we used as control. Among the tested gold(III) complexes, [Au(en)Cl 2] +was the least cytotoxic to BCL-1 cells. In line with the obtained results, we suggest that the [Au(bipy)Cl 2] + complex should be tested in vivo in experimental models of B cell leukaemia

Studies of the stability, nucleophilic substitution reactions, DNA/BSA interactions, cytotoxic activity, DFT and molecular docking of some tetra- and penta-coordinated gold(iii) complexes

Two gold(III) complexes, square-planar [Au(DPP)Cl2]+(1) and distorted square-pyramidal [Au(DMP)Cl3] (2) (where DMP = 2,9-dimethyl-1,10-phenanthroline and DPP = 4,7-diphenyl-1,10-phenanthroline), were studied by different experimental methods. Their stability in water and in buffer solution (25 mM Hepes, 30 mM NaCl, pH = 7.2) was investigated by UV-Vis spectroscopy while their redox stability is confirmed by CV. Substitution reactions between complexes 1 and 2, and biologically relevant ligands, such as thiourea (Tu), guanosine-5′-monophosphate (5′-GMP), glutathione (GSH) and L-methionine (L-Met), were studied by a stopped-flow technique, under the pseudo-first order conditions as a function of ligand concentration and temperature. According to the values of the activation parameters, all studied reactions followed an associative substitution mechanism. DNA binding studies of complexes 1 and 2 were performed by UV-Vis and fluorescence spectroscopy and viscosity measurements, as well as interactions with bovine serum albumin (BSA). Density functional theory (DFT) was implemented in order to analyse the wave function of the optimized structures to get better insight into the binding interactions between the inert ligands and gold(III) center. The experimental results of binding studies with DNA and BSA were simulated and compared by performing a molecular docking study. All results demonstrate the strong connection between the reactivity of the complexes toward biologically important targets and their structural and electronic characteristics. The cytotoxic activity of complexes 1 and 2 against different cell lines (MDA-MB-231, HCT-116, and HaCaT) was evaluated 24 and 72 h after treatments. The results indicate reduced viability of cell lines in a time- and dose-dependent manner.Accepted for publishin