Aromatic Amine N-oxide Metal Complexes Bearing High Anti Trypanosoma Cruzi In Vitro Activity

M. VIEITES; BEATRIZ PARAJÓN-COSTA; L.OTERO; C.OLEA-AZAR; J.RODRIGUEZ; V.GALAZ; G.AGUIRRE; M.GONZALEZ; H.CERECETTO; P.SMIRCICH; A.G.BARRIO; B.GARAT; D.GAMBINO

Sao-Pablo, Brasil

Simposio; The 3rd Brazilian Symposium on Medicinal Chemistry; 2006

Chagas´ disease (American Trypanosomiasis) is the largest parasitic disease burden in the American continent. The many activities of metal ions in biology have stimulated in the last decades the development of metal-based chemotherapeutics in different fields of medicine. In the search for new therapeutic tools against Chagas´ disease, our group has successfully used the approach based on the synthesis of coordination compounds of organic ligands bearing antitrypanosomal activity with pharmacologically active metals. In the present work palladium and platinum were selected because of the metabolic similarities between tumor cells and Trypanosoma cruzi and their proved ability to bind DNA as main antitumoral mechanism of action. Complexes with the bioactive compound 2-mercaptopyridine N-oxide (L) as ligand were characterized by different techniques and their mode of action was investigated (DNA interaction, free radicals production). Pd and Pt complexes showed excellent in vitro growth inhibition activity against Trypanosoma cruzi (IC50 67 and 200 nM, respectively) and non unspecific cytotoxicity against macrophages. [Pt(L)2] showed the highest selectivity index (>>10).