Water-Soluble Ruthenium (II) Chiral Heteroleptic Complexes with Amoebicidal in Vitro and in Vivo Activity
Por:
Toledano-Magana, Yanis, Garcia-Ramos, Juan C., Torres-Gutierrez, Carolina, Vazquez-Gasser, Cristina, Esquivel-Sanchez, Jose M., Flores-Alamo, Marcos, Ortiz-Frade, Luis, Galindo-Murillo, Rodrigo, Nequiz, Mario, Gudino-Zayas, Marco, Laclette, Juan P., Carrero, Julio C., Ruiz-Azuara, Lena
Publicada:
9 feb 2017
Resumen:
Three water-soluble Ru(II) chiral heteroleptic coordination compounds
[Ru(en)(pdto)]Cl-2 (1), [110(gly)(pdto)]Cl (2),, and
[Ru(acac)(pdto)]Cl (3), where pdto
2,2'-[1,2-ethanediylbis-(sulfanecliy1-2,1-ethanediyO]dipyridine, en =
ethylendiamine, gly = glycinate, and acac = acetylacetonate, have been
synthezised and fully characterized. The crystal structures of compounds
1-3 are described. The IC50 values 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 mu M).
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.
Filiaciones:
Univ Nacl Autonoma Mexico, Fac Quim, Dept Quim Inorgan & Nucl, Ave Univ 3000, Mexico City 04510, DF, Mexico
UNAM, CONACYT, Ctr Nanociencias & Nanotecnol, Km 107 Carretera Tijuana Ensenada, Ensenada 22860, Baja California, Mexico
Univ Nacl Autonoma Mexico, Inst Quim, Dept Fisicoquim, Ave Univ 3000, Mexico City 04510, DF, Mexico
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Dept Inmunol, Ave Univ 3000, Mexico City 04510, DF, Mexico
Ctr Invest & Desarrollo Tecnol Electroquim SC, Dept Electroquim, Parque Tecnol Queretaro Sanfandila, Pedro De Escobedo 76703, Queretaro, Mexico
Univ Utah, Dept Med Chem, Coll Pharm, Skaggs Hall 201, Salt Lake City, UT 84112 USA
Univ Nacl Autonoma Mexico, Fac Med, Dept Expt Med, Dr Balmis 148,Col Doctores, Mexico City 06726, DF, Mexico
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