Cytotoxicity of (2,2 ': 6 ',2 '' terpyridine) platinum(II) complexes to Leishmania donovani, Trypanosoma cruzi, and Trypanosoma brucei

A range of (2,2':6',2 "-terpyridine)platinum(II) complexes are shown to pos sess antiprotozoal activity in vitro against Leishmania donovani, Trypanoso ma cruzi, and Trypanosoma brucei, the causative organisms of tropical disea ses leishmaniasis and trypanosomiasis. The best compounds caused 100% and 7 8% inhibition of growth of the intracellular amastigote forms of L. donovan i and T. cruzi, respectively, at a concentration of 1 mu M and 100% inhibit ion of growth of the bloodstream trypomastigote forms of T. brucei at a con centration of 0.03 mu M. The results obtained with complexes in which the f ourth ligand to platinum(II) is capable of being substituted with a substit ution inert hydroxyethanethiolate complex are compared. The ammine complexe s show high antiprotozoal activity suggesting that the trans influence of t he 2,2': 6',2 "-terpyridine ligand has a profound effect on the ease of dis placement of the fourth ligand in (2,2':6',2 "-terpyridine)platinum(II) com plexes, although nonbonded interaction between the ammine ligand and the 6 and 6 " hydrogens probably also weakens the ligation to Pt(II).