CEQUINOR   05415
CENTRO DE QUIMICA INORGANICA "DR. PEDRO J. AYMONINO"
Unidad Ejecutora - UE
artículos
Título:
Risedronate metal complexes potentially active against Chagas disease
Autor/es:
B.DEMORO; F.CARUSO; M.ROSSI; D.BENÍTEZ; M.GONZALEZ; H.CERECETTO; B.PARAJÓN-COSTA; J.CASTIGLIONI; M. GALIZZI,; R. DOCAMPO; L.OTERO; D.GAMBINO
Revista:
JOURNAL OF INORGANIC BIOCHEMISTRY
Editorial:
ELSEVIER SCIENCE INC
Referencias:
Año: 2010 vol. 104 p. 1252 - 1252
ISSN:
0162-0134
Resumen:
In the search for new metal-based drugs for the treatment of Chagas disease, the most widespread Latin American parasitic disease, novel complexes of the bioactive ligand risedronate (Ris, (1-hydroxy-1-phosphono-2-pyridin-3-yl-ethyl)phosphonate), [MII(Ris)2]·4H2O, where M Cu, Co, Mn and Ni, and [NiII(Ris)2(H2O)2]·H2O were synthesized and characterized by using analytical measurements, thermogravimetric analyses, cyclic voltammetry and infrared and Raman spectroscopies. Crystal structures of [CuII(Ris)2]·4H2O and [NiII(Ris)2(H2O)2]·H2O were solved by single crystal X-ray diffraction methods. The complexes, as well as the free ligand, were evaluated in vitro against epimastigotes and intracellular amastigotes of the parasiteTrypanosoma cruzi, causative agent of Chagas disease. Results demonstrated that the coordination of risedronate to different metal ions improved the antiproliferative effect against T. cruzi, exhibiting growth inhibition values against the intracellular amastigotes ranging the low micromolar levels. In addition, this strong activity could be related to high inhibition of farnesyl diphosphate synthase enzyme. On the other hand, protein interaction studies showed that all the complexes strongly interact with albumin thus providing a suitable means of transporting them to tissues in vivo.