Tumor cytotoxicity of 5,6-dimethyl-1,10-phenanthroline and its corresponding gold(III) complex

A gold(III) complex possessing 5,6-dimethyl-1,10-phenanthroline (5,6DMP) was synthesized and fully characterized using standard spectroscopic techniques, as well as X-ray crystallography and elemental analysis. The complex [(5,6DMP)AuCl2][BF4] (2) was found to possess a distorted square planar geometry about the gold(III) center, commonplace for d8 Au(III) cations possessing sterically un-hindered polypyridyl ligands. Compound 2 was evaluated for its potential use as an anticancer therapeutic. It was determined that the complex is stable in phosphate buffer over a 24-hour period, thought it does undergo rapid reduction in the presence of equimolar amounts of reduced glutathione (GSH) and ascorbic acid. The DNA binding and in vitro tumor cytotoxicity of the title compound 2 were also determined. It was found to undergo weak and reversible binding to calf thymus DNA, and was more cytotoxic towards a panel of human cancer cell lines than the commonly used chemotherapy agent cisplatin. Cytotoxicity experiments with the free 5,6DMP ligand indicate that the ligand has IC50 values that are slightly lower than those observed for the gold complex (2), and coupled with the fact that the ligand appears to be released from the gold(III) metal center in reducing environments, this suggests the ligand itself may play an important role in the antitumor activity of the parent gold complex.

Graphical AbstractBoth the gold(III) complex ion, [(5,6DMP)AuCl2]+, and the free 5,6DMP ligand are found to be more cytotoxic than cisplatin against in vitro lung and head–neck tumor cell lines. Stability experiments also indicate that the ligand is released upon the reduction of the gold(III) metal center. These results agree with previous studies involving gold(III) polypyridyl complexes, and highlight the need to determine whether the gold(III) complex or the free ligand act as the cytotoxic agent.Figure optionsDownload full-size imageDownload as PowerPoint slide