Antitumor activity of titanocene amino acid complexes.

Seven ionic titanocene alpha-amino acid (aa) complexes [(C5H5)2Ti(aa)2]2+[X]2- with aa = glycine, L-alanine, 2-methylalanine, D-L-phenylalanine, D,L-4-fluorophenylalanine and X = Cl or AsF6, were investigated for antitumor activity against fluid Ehrlich ascites tumor growing in CF1 mice. These complexes are the first stable model compounds of titanocene units with protein components, synthesized from a water-like, methanolic medium. All titanocene amino acid complexes induced antitumor activity which was manifested by maximum cure rates ranging from 30 to 70% and increases in life span from 78 to 276% in comparison with untreated control animals. The complexes containing chloride as anion X were more effective than the hexafluoroarsenate derivatives, which surprisingly showed a low substance toxicity. In all cases, the antitumor activity of the ionic titanocene amino acid complexes tested was less pronounced than that of the neutral parent compound [(C5H5)2TiCl2].