title: Water-Soluble Ruthenium (II) Chiral Heteroleptic Complexes with Amoebicidal in Vitro and in Vivo Activity.
abstract: Three water-soluble Ru(II) chiral heteroleptic coordination compounds [Ru(en)(pdto)]Cl2(1), [Ru(gly)(pdto)]Cl (2), and [Ru(acac)(pdto)]Cl (3), where pdto = 2,2'-[1,2-ethanediylbis-(sulfanediyl-2,1-ethanediyl)]dipyridine, en = ethylendiamine, gly = glycinate, and acac = acetylacetonate, have been synthezised and fully characterized. The crystal structures of compounds 1-3 are described. The IC50values for compounds 1-3 are within nanomolar range (14, 12, and 6 nM, respectively). The cytotoxicity for human peripheral blood lymphocytes is extremely low (>100 μM). Selectivity indexes for Ru(II) compounds are in the range 700-1300. Trophozoites exposed to Ru(II) compounds die through an apoptotic pathway triggered by ROS production. The orally administration to infected mice induces a total elimination of the parasite charge in mice faeces 1-2-fold faster than metronidazole. Besides, all compounds inhibit the trophozoite proliferation in amoebic liver abscess induced in hamster. All our results lead us to propose these compounds as promising candidates as antiparasitic agents.
authors.affiliation: Departamento de Química Inorgánica y Nuclear, Facultad de Química, Universidad Nacional Autónoma de México , Avenida Universidad 3000, 04510, Mexico City, Mexico.
authors.forename: Yanis
authors.initials: Y
authors.lastname: Toledano-Magaña
authors.affiliation: Departamento de Química Inorgánica y Nuclear, Facultad de Química, Universidad Nacional Autónoma de México , Avenida Universidad 3000, 04510, Mexico City, Mexico.|Departamento de Fisicoquímica, Instituto de Química, Universidad Nacional Autónoma de México , Avenida Universidad 3000, 04510, Mexico City, Mexico.
authors.forename: Juan C
authors.initials: JC
authors.lastname: García-Ramos
authors.affiliation: Departamento de Química Inorgánica y Nuclear, Facultad de Química, Universidad Nacional Autónoma de México , Avenida Universidad 3000, 04510, Mexico City, Mexico.
authors.forename: Carolina
authors.initials: C
authors.lastname: Torres-Gutiérrez
authors.affiliation: Departamento de Química Inorgánica y Nuclear, Facultad de Química, Universidad Nacional Autónoma de México , Avenida Universidad 3000, 04510, Mexico City, Mexico.
authors.forename: Cristina
authors.initials: C
authors.lastname: Vázquez-Gasser
authors.affiliation: Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México , Avenida Universidad 3000, 04510, Mexico City, Mexico.
authors.forename: José M
authors.initials: JM
authors.lastname: Esquivel-Sánchez
authors.affiliation: Departamento de Química Inorgánica y Nuclear, Facultad de Química, Universidad Nacional Autónoma de México , Avenida Universidad 3000, 04510, Mexico City, Mexico.
authors.forename: Marcos
authors.initials: M
authors.lastname: Flores-Alamo
authors.affiliation: Departamento de Electroquímica, Centro de Investigación y Desarrollo Tecnológico en Electroquímica SC , Parque Tecnológico Querétaro Sanfandila, Pedro de Escobedo, CP 76703 Querétaro México.
authors.forename: Luis
authors.initials: L
authors.lastname: Ortiz-Frade
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Utah , Skaggs Hall 201, Salt Lake City, Utah 84112, United States.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Galindo-Murillo
authors.affiliation: Departamento de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México , Dr. Balmis 148, Col. Doctores, 06726, Mexico City, Mexico.
authors.forename: Mario
authors.initials: M
authors.lastname: Nequiz
authors.affiliation: Departamento de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México , Dr. Balmis 148, Col. Doctores, 06726, Mexico City, Mexico.
authors.forename: Marco
authors.initials: M
authors.lastname: Gudiño-Zayas
authors.affiliation: Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México , Avenida Universidad 3000, 04510, Mexico City, Mexico.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Laclette
authors.affiliation: Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México , Avenida Universidad 3000, 04510, Mexico City, Mexico.
authors.forename: Julio C
authors.initials: JC
authors.lastname: Carrero
authors.affiliation: Departamento de Química Inorgánica y Nuclear, Facultad de Química, Universidad Nacional Autónoma de México , Avenida Universidad 3000, 04510, Mexico City, Mexico.
authors.forename: Lena
authors.identifier: 0000-0003-3035-4507
authors.initials: L
authors.lastname: Ruiz-Azuara
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D018360:Crystallography, X-Ray; D004748:Entamoeba histolytica / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D008101:Liver Abscess, Amebic / Q000188:drug therapy; D051379:Mice; D017382:Reactive Oxygen Species / Q000378:metabolism; D017975:Ruthenium Compounds / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D013237:Stereoisomerism
chemical_list: D000981:Antiprotozoal Agents; D017382:Reactive Oxygen Species; D017975:Ruthenium Compounds