Cytotoxicity of (2,2‘:6‘,2‘ ‘-Terpyridine)platinum(II) Complexes to Leishmania d onovani, Trypanosoma c ruzi, and Trypanosoma b rucei

• Published in: Journal of medicinal chemistry 1999-03, Vol.42 (6), p.999-1006
• Main Authors: Lowe, Gordon, Droz, Anne Sophie, Vilaivan, Tirayut, Weaver, George W, Tweedale, Lindsay, Pratt, Jonathan M, Rock, Peter, Yardley, Vanessa, Croft, Simon L
• Format: Article
• Language: English
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm981074c

A range of (2,2‘:6‘,2‘ ‘-terpyridine)platinum(II) complexes are shown to possess antiprotozoal activity in vitro against Leishmania donovani, Trypanosoma cruzi, and Trypanosoma brucei, the causative organisms of tropical diseases leishmaniasis and trypanosomiasis. The best compounds caused 100% and 78% inhibition of growth of the intracellular amastigote forms of L. donovani and T. cruzi, respectively, at a concentration of 1 μM and 100% inhibition of growth of the bloodstream trypomastigote forms of T. brucei at a concentration of 0.03 μM. The results obtained with complexes in which the fourth ligand to platinum(II) is capable of being substituted with a substitution inert hydroxyethanethiolate complex are compared. The ammine complexes show high antiprotozoal activity suggesting that the trans influence of the 2,2‘:6‘,2‘ ‘-terpyridine ligand has a profound effect on the ease of displacement of the fourth ligand in (2,2‘:6‘,2‘ ‘-terpyridine)platinum(II) complexes, although nonbonded interaction between the ammine ligand and the 6 and 6‘ ‘ hydrogens probably also weakens the ligation to Pt(II).