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Water-Soluble Ruthenium (II) Chiral Heteroleptic Complexes With Amoebicidal in Vitro and in Vivo Activity

Water-Soluble Ruthenium (II) Chiral Heteroleptic Complexes With Amoebicidal in Vitro and in Vivo Activity

Yanis Toledano-Magaña, Juan C García-Ramos, Carolina Torres-Gutiérrez, Cristina Vázquez-Gasser, José M Esquivel-Sánchez, Marcos Flores-Alamo, Luis Ortiz-Frade, Rodrigo Galindo-Murillo, Mario Nequiz, Marco Gudiño-Zayas, etc.

J Med Chem. 2017 Feb 9;60(3):899-912.

PMID: 28075589

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 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 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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP15282889	Lead(II) acetylacetonate		15282-88-9	Price

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