Tuning the Anticancer Activity of Gold(I) Complexes via Redox-Active Ar-Bian Ligands: Experimental and Theoretical...

A series of cationic gold(I) complexes of the type [Au(PPh3)(Ar-Bian)](CF3SO3) based on 1,2-bis[(2,4,6-trimethylphenyl)imino]acenaphthene (tmp-Bian), 1,2-bis[(4-chlorophenyl)imino]acenaphthene (4-Cl-C6H4-Bian), 1,2-bis[(4-bromophenyl)imino]acenaphthene (4-Br-C6H4-Bian), and 1,2-bis[(4-iodophenyl)imino]acenaphthene (4-I-C6H4-Bian) were prepared. All complexes were fully characterized by spectrochemical methods, and their crystal structures were established by X-ray diffraction analysis. The electrochemical behavior of all complexes was studied by using cyclic voltammetry. The stability of the complexes in solution was investigated using 1H NMR and UV-vis spectroscopies. The anticancer activity of Au(I) complexes was evaluated against a panel of cell lines in comparison with free 1,2-bis(arylimino)aceaphthenes (Ar-Bian) and initial [Au(PPh3)Cl]. All complexes were cytotoxic in a low micromolar range and showed selectivity toward cancer cells in comparison with MRC-5 human lung fibroblasts. The ability of the complexes to bind DNA and BSA was investigated by spectroscopic methods, molecular docking, and molecular dynamics studies. The DNA-damaging activity of gold(I) complexes was evaluated in MCF-7 cells using the comet assay. Reactive oxygen species production in MCF-7 cells was studied using confocal microscopy. The lipophilicity of complexes was determined using the n-octanol/water shake-flask method. Determination of the cell death pathway was performed using an Annexin-5-FITC/PI double staining test followed by fluorescence-activated cell sorting (FACS) analysis.