Mechanistic and cytotoxicity studies of group IV ß-diketonate complexes.

ABSTRACT

Group IV metal complexes have previously shown promise as novel anticancer agents. Here, we discuss the mechanistic and cytotoxic nature of a series of group IV ß-diketonate coordination complexes. Clear evidence that the ligands are exchangeable on the metal centre and that the ß-diketonate ligands can act as potential drug delivery vehicles of the group IV metal ions was obtained. When evaluated for the cytotoxicity against human colon adenocarcinoma (HT-29) and human breast adenocarcinoma (MCF-7) cell lines, a general trend of decreasing potency down the group IV metals was observed. The most promising results obtained were for the hafnium complexes, with the tris diphenyl ß-diketonate hafnium complex exhibiting IC50 values of 4.9 ± 0.9 µM and 3.2 ± 0.3 µM against HT-29 and MCF-7, respectively, which are comparable with the activity of cisplatin against the same cell lines. This tri ß-diketonate hafnium complex is the first to show potent in vitro cytotoxic activity. The results reported show that ligand design has a significant effect on the cytotoxic potential of the complexes, and that these group IV complexes warrant further evaluation as novel metal-containing anticancer agents.