Risedronate metal complexes potentially active against Chagas disease.

Abstract

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), [M(II)(Ris)(2)]·4H(2)O, where M═Cu, Co, Mn and Ni, and [Ni(II)(Ris)(2)(H(2)O)(2)]·H(2)O were synthesized and characterized by using analytical measurements, thermogravimetric analyses, cyclic voltammetry and infrared and Raman spectroscopies. Crystal structures of [Cu(II)(Ris)(2)]·4H(2)O and [Ni(II)(Ris)(2)(H(2)O)(2)]·H(2)O 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 parasite Trypanosoma 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.

• Authors: Bruno Demoro, Francesco Caruso, Miriam Rossi, Diego Benítez, Mercedes Gonzalez, Hugo Cerecetto, Beatriz Parajón-Costa, Jorge Castiglioni, Melina Galizzi, Roberto Docampo, Lucía Otero, Dinorah Gambino
• Journal: Journal of inorganic biochemistry (J Inorg Biochem) Vol. 104 Issue 12 Pg. 1252-8 (Dec 2010) ISSN: 1873-3344 [Electronic] United States
• PMID: 20817265 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Inc. All rights reserved.

Chemical References

• Coordination Complexes
• Geranyltranstransferase
• Risedronic Acid
• Etidronic Acid

Topics

• Animals
• Chagas Disease (drug therapy)
• Coordination Complexes (chemistry, therapeutic use)
• Etidronic Acid (analogs & derivatives, chemistry, therapeutic use)
• Geranyltranstransferase (metabolism)
• Models, Chemical
• Risedronic Acid
• Trypanosoma cruzi (drug effects, metabolism, pathogenicity)
• X-Ray Diffraction