Bisphosphonate metal complexes as selective inhibitors of Trypanosoma cruzi farnesyl diphosphate synthase. (Articolo in rivista)

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  • Bisphosphonate metal complexes as selective inhibitors of Trypanosoma cruzi farnesyl diphosphate synthase. (Articolo in rivista) (literal)
Anno
  • 2012-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1039/C2DT12179D (literal)
Alternative label
  • Bruno Demoro, Francesco Caruso, Miriam Rossi, Diego Benítez, Mercedes González, Hugo Cerecetto, Melina Galizzi, Leena Malayil, Roberto Docampo, Ricardo Faccio, Álvaro W. Mombrú, Dinorah Gambino, Lucía Otero (2012)
    Bisphosphonate metal complexes as selective inhibitors of Trypanosoma cruzi farnesyl diphosphate synthase.
    in Dalton transactions (2003. Print)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Bruno Demoro, Francesco Caruso, Miriam Rossi, Diego Benítez, Mercedes González, Hugo Cerecetto, Melina Galizzi, Leena Malayil, Roberto Docampo, Ricardo Faccio, Álvaro W. Mombrú, Dinorah Gambino, Lucía Otero (literal)
Pagina inizio
  • 6468 (literal)
Pagina fine
  • 6476 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#url
  • http://pubs.rsc.org/en/content/articlelanding/2012/dt/c2dt12179d (literal)
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  • 41 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali
  • 9 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 21 (literal)
Note
  • PubMe (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Cátedra de Química Inorgánica, DEC, Facultad de Química, Universidad de la República, Gral. Flores 2124, C. C. 1157, 11800 Montevideo, Uruguay; Istituto Chimica Biomolecolare, CNR, Ple. Aldo Moro, 5, 00185 Rome, Italy; Department of Chemistry, Vassar College, Poughkeepsie, New York 12604-0484, USA; Grupo de Química Medicinal, Facultad de Química-Facultad de Ciencias, Universidad de la República, Iguá 4225, Montevideo, Uruguay; Center for Tropical and Emerging Global Diseases and Department of Cellular Biology, University of Georgia, Athens, USA; Centro NanoMat&Cryssmat-lab. DETEMA. Facultad de Química,Universidad de la República, Gral. Flores 2124, C. C. 1157, 11800 Montevideo, Uruguay. (literal)
Titolo
  • Bisphosphonate metal complexes as selective inhibitors of Trypanosoma cruzi farnesyl diphosphate synthase. (literal)
Abstract
  • In the search for a pharmacological answer to treat Chagas disease, eight metal complexes with two bioactive bisphosphonates, alendronate (Ale) and pamidronate (Pam), were described. Complexes of the formula [M(2)(II)(Ale)(4)(H(2)O)(2)]·2H(2)O, with M = Cu, Co, Mn, Ni, and ([CuPam]·H(2)O)(n) as well as [M(II)(Pam)(2)(H(2)O)(2)]·3H(2)O, with M = Co, Mn and Ni, were synthesized and fully characterized. Crystal structure of [Cu(2)(II)(Ale)(4)(H(2)O)(2)]·2H(2)O, [Co(II)(Pam)(2)(H(2)O)(2)] and [Ni(II)(Pam)(2)(H(2)O)(2)] were solved by X-ray single crystal diffraction methods and the structures of [M(2)(II)(Ale)(4)(H(2)O)(2)]·2H(2)O complexes M = Co, Mn and Ni were studied by X-ray powder diffraction methods. All obtained complexes were active against the amastigote form of Trypanosoma cruzi (T. cruzi), etiological agent of Chagas disease. Most of them were more active than the corresponding free ligands showing no toxicity for mammalian cells. The main mechanism of the antiparasitic action of bisphosphonates, inhibition of parasitic farnesyl diphosphate synthase (TcFPPS), remains in the obtained metal complexes and an increase in the inhibiting enzyme levels was observed upon coordination. Observed enzymatic inhibition was selective for TcFPPS as the metal complexes showed no or little inhibition of human FPPS. Additionally, metal complexation might improve the bioavailability of the complexes through the hindrance of the phosphonate group's ionization at physiological pH and, eventually, through the ability of plasma proteins to work as complex transporters. (literal)
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