Bisphosphonate metal complexes as selective inhibitors of Trypanosoma cruzi farnesyl diphosphate synthase

Dalton Transactions : an International Journal of Inorganic Chemistry
Bruno DemoroLucía Otero

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...Continue Reading

References

Jan 1, 1985·Methods in Enzymology·H C Rilling
Jan 1, 1985·Methods in Enzymology·G F Barnard
Jul 4, 2001·The Journal of Biological Chemistry·A MontalvettiR Docampo
Mar 19, 2002·Journal of Inorganic Biochemistry·Rachael C DolmanTrevor W Hambley
Nov 29, 2002·Current Drug Targets. Infectious Disorders·R Docampo, S N Moreno
Oct 29, 2003·Trends in Parasitology·Julio A Urbina, Roberto Docampo
Dec 16, 2003·The Journal of Biological Chemistry·David J HosfieldJohn Finn
Feb 3, 2004·Mini Reviews in Medicinal Chemistry·Roberto A Sánchez-Delgado, Atilio Anzellotti
Apr 10, 2004·European Journal of Medicinal Chemistry·Eliana CabreraAntonio Monge
May 11, 2006·Proceedings of the National Academy of Sciences of the United States of America·Kathryn L KavanaghUdo Oppermann
Jul 11, 2006·European Journal of Medicinal Chemistry·Lucía OteroHugo Cerecetto
Aug 8, 2006·ChemMedChem·Jean-Michel RondeauWolfgang Jahnke
Oct 10, 2006·Journal of Inorganic Biochemistry·Lucía OteroBeatriz Garat
Sep 18, 2007·Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy·Lucía OteroClaudio Olea-Azar
Nov 10, 2007·Dalton Transactions : an International Journal of Inorganic Chemistry·Trevor W Hambley
Dec 25, 2007·Acta Crystallographica. Section A, Foundations of Crystallography·George M Sheldrick
Jan 30, 2008·Journal of Inorganic Biochemistry·Marisol VieitesDinorah Gambino
Mar 7, 2008·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Marisol VieitesDinorah Gambino
May 14, 2008·Current Pharmaceutical Design·Roberto Docampo, Silvia N J Moreno
Aug 8, 2008·Journal of Inorganic Biochemistry·Simon P FrickerJames H McKerrow
Dec 19, 2008·Journal of Inorganic Biochemistry·Julio BenítezDinorah Gambino
Jun 25, 2009·Current Medicinal Chemistry·Gildardo RiveraAntonio Monge
Nov 26, 2009·Acta Tropica·Gabriel A Schmunis, Zaida E Yadon
Apr 20, 2010·Lancet·Anis RassiJosé Antonio Marin-Neto
Jun 22, 2010·Accounts of Chemical Research·Eric Oldfield
Jul 21, 2010·PLoS Neglected Tropical Diseases·Adriana M C CanavaciRick L Tarleton
Sep 8, 2010·Journal of Inorganic Biochemistry·Bruno DemoroDinorah Gambino
Nov 30, 2010·Bone·Michael J RogersJukka Mönkkönen
Jul 26, 2011·Journal of Medicinal Chemistry·Artur MuchaŁukasz Berlicki
Aug 23, 2011·Current Opinion in Infectious Diseases·Guillaume Le LoupFrançois Xavier Lescure
Dec 6, 2011·Dalton Transactions : an International Journal of Inorganic Chemistry·Bruno DemoroDinorah Gambino

❮ Previous
Next ❯

Citations

Jan 29, 2013·European Journal of Medicinal Chemistry·Julio BenítezDinorah Gambino
Apr 11, 2014·Expert Review of Clinical Pharmacology·Juan M Bustamante, Rick L Tarleton
Apr 2, 2016·Oxidative Medicine and Cellular Longevity·Amy T ChristensenMarjorie A Jones
Jun 30, 2015·Chemical Reviews·Joydeb Goura, Vadapalli Chandrasekhar
Dec 21, 2018·Chemical Communications : Chem Comm·Agnes E Thorarinsdottir, T David Harris
Jan 20, 2018·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Bruno DemoroLucía Otero
Jul 1, 2017·PLoS Neglected Tropical Diseases·Leah M WachsmuthJason Gavenonis
Apr 2, 2020·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Micaella CiprianiLucía Otero
Aug 8, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Violeta KourbeliIoannis P Papanastasiou

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antiparasitics

Antiparasitics are medications which are indicated for the treatment of parasitic diseases. Discover the latest research on antiparasitics here.