Organometallic Chemistry Research Papers - Academia.edu (original) (raw)

Cisplatin [cis-diamminedichloroplatinum-(II)] has been used since 1978 to treat a number of different cancer cell lines. However, its effectiveness has been limited due to both harmful side effects as well as the development of cisplatin resistant cancers. Thus, alternatives to cisplatin have become an important focus in anti-cancer research. Gold-(III), an isoelectronic species to platinum-(II), has been of focus to us because of its ability to form metal complexes with similar geometries to platinum-(II) complexes. Previously, 2-sec-butyl-1,10-phenanthroline (sec-butylphen) and its corresponding [(sec-butylphen)AuCl3] complex were synthesized and their anticancer properties subsequently characterized by means of in-vitro tumor cytotoxicity studies. These studies showed a significantly higher cytotoxicity for the sec-butylphen ligand and gold-(III) complex than cisplatin. In addition, when the IC50 values of the free ligand and gold-(III) complex were compared, it was revealed that the free ligand was more cytotoxic, suggesting that it is more active in tumor cell death. In order to determine if gold-(III) complexes have a distinct mechanism for killing cancer cells, structural analogues were synthesized: 2-methyl-9-sec-butyl-1,10-phenanthroline, 2,9-di-sec-butyl-1,10-phenanthroline, and 2,9-di-methyl-1,10-phenanthroline, as well as their corresponding gold-(III) complexes. Their structures were verified using 1H NMR, X-ray crystallography, and elemental analysis. SRB cytotoxicity studies revealed that both ligand and gold-(III) complexes displayed greater cytotoxicity than cisplatin. The data also indicated that the gold-(III) complex antitumor activity does not change as a function of ligand IC50, suggesting that the gold-(III) complexes have a distinct mechanism of tumor cell death. Current research in our laboratory is focused on mono-substituted analogues of 1,10-phenanthroline. 2-n-butyl-1,10-phenanthroline and its gold-(III) complex have been synthesized and their structures have been verified by means of 1H NMR and X-ray crystallography. Elemental analysis, as well as GSH and SRB studies are currently underway.