Activity on Trypanosoma cruzi, erythrocytes lysis and biologically relevant physicochemical properties of Pd(II) and Pt(II) complexes of thiosemicarbazones derived from 1-indanones

D. SANTOS, B. PARAJÓN-COST, M. ROSSI, F. CARUSO, D. BENÍTEZ, J. VARELA, H. CERECETTO, M. GONZÁLEZ, N. GÓMEZ, M. E. CAPUTTO, A. G. MOGLIONI, G. Y. MOLTRASIO, L. M. FINKIELSZTEIN, D. GAMBINO

JOURNAL OF INORGANIC BIOCHEMISTRY

ELSEVIER SCIENCE INC

Lugar: Amsterdam; Año: 2012 vol. 117 p. 270 - 276

0162-0134

American trypanosomiasis or Chagas disease, caused by the protist parasite Trypanosoma cruzi (T. cruzi), is amajor health concern in Latin America. In the search for new bioactive compounds, eight Pd(II) and Pt(II)complexes of thiosemicarbazones derived from 1-indanones (HL) were evaluated as potential anti-T. cruzicompounds. Their unspecific cytotoxicity was determined on human erythrocytes. Two physicochemical features,lipophilicity and redox behavior, that could be potentially relevant for the biological activity of thesecomplexes, were determined. Crystal structure of [Pd(HL1)(L1)]Cl·CH3OH, where HL1=1-indanonethiosemicarbazone, was solved by X-ray diffraction methods. Five of the eight metal complexes showed activityagainst T. cruzi with IC50 values in the low micromolar range and showed significantly higher activitythan the corresponding free ligands. Four of them resulted more active against the parasite than the referenceantitrypanosomal drug Nifurtimox. Anti-T. cruzi activity and selectivity towards the parasite were bothhigher for the Pd(II) compounds than for the Pt(II) analogues, showing the effect of the metal center selectionon the biological behavior. Among both physicochemical features tested for this series of compounds, lipophilicityand redox behavior, only the former seemed to show correlation with the antiproliferative effectsobserved. Metal coordination improved bioactivity but lead to an increase of mammalian cytotoxicity. Nevertheless,some of the metal complexes tested in this work still show suitable selectivity indexes and deservefurther developments.