title: Water-soluble ruthenium complexes bearing activity against protozoan parasites.
abstract: Parasitic illnesses are major causes of human disease and misery worldwide. Among them, both amebiasis and Chagas disease, caused by the protozoan parasites, Entamoeba histolytica and Trypanosoma cruzi, are responsible for thousands of annual deaths. The lack of safe and effective chemotherapy and/or the appearance of current drug resistance make the development of novel pharmacological tools for their treatment relevant. In this sense, within the framework of the medicinal inorganic chemistry, metal-based drugs appear to be a good alternative to find a pharmacological answer to parasitic diseases. In this work, novel ruthenium complexes [RuCl2(HL)(HPTA)2]Cl2 with HL=bioactive 5-nitrofuryl containing thiosemicarbazones and PTA=1,3,5-triaza-7-phosphaadamantane have been synthesized and fully characterized. PTA was included as co-ligand in order to modulate complexes aqueous solubility. In fact, obtained complexes were water soluble. Their activity against T. cruzi and E. histolytica was evaluated in vitro. [RuCl2(HL4)(HPTA)2]Cl2 complex, with HL4=N-phenyl-5-nitrofuryl-thiosemicarbazone, was the most active compound against both parasites. In particular, it showed an excellent activity against E. histolytica (half maximal inhibitory concentration (IC50)=5.2 μM), even higher than that of the reference drug metronidazole. In addition, this complex turns out to be selective for E. histolytica (selectivity index (SI)>38). The potential mechanism of antiparasitic action of the obtained ruthenium complexes could involve oxidative stress for both parasites. Additionally, complexes could interact with DNA as second potential target by an intercalative-like mode. Obtained results could be considered a contribution in the search for metal compounds that could be active against multiple parasites.
authors.affiliation: Cátedra de Química Inorgánica, DEC, Facultad de Química, Universidad de la República, Gral. Flores 2124, C. C. 1157, 11800, Montevideo, Uruguay.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Sarniguet
authors.forename: Jeannette
authors.initials: J
authors.lastname: Toloza
authors.forename: Micaella
authors.initials: M
authors.lastname: Cipriani
authors.forename: Michel
authors.initials: M
authors.lastname: Lapier
authors.forename: Marisol
authors.initials: M
authors.lastname: Vieites
authors.forename: Yanis
authors.initials: Y
authors.lastname: Toledano-Magaña
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: García-Ramos
authors.forename: Lena
authors.initials: L
authors.lastname: Ruiz-Azuara
authors.forename: Virtudes
authors.initials: V
authors.lastname: Moreno
authors.forename: Juan Diego
authors.initials: JD
authors.lastname: Maya
authors.forename: Claudio Olea
authors.initials: CO
authors.lastname: Azar
authors.forename: Dinorah
authors.initials: D
authors.lastname: Gambino
authors.forename: Lucía
authors.initials: L
authors.lastname: Otero
mesh_terms: D000818:Animals; D015394:Molecular Structure; D012428:Ruthenium / Q000737:chemistry*; D013882:Thiosemicarbazones / Q000737:chemistry; D014344:Trypanocidal Agents / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
chemical_list: D013882:Thiosemicarbazones; D014344:Trypanocidal Agents; D014867:Water; D012428:Ruthenium