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

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• 作者：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 ; Juan P. Laclette ; Julio C. Carrero ; Lena Ruiz-Azuara
• 刊名：Journal of Medicinal Chemistry
• 出版年：2017
• 出版时间：February 9, 2017
• 年：2017
• 卷：60
• 期：3
• 页码：899-912
• 全文大小：744K
• ISSN：1520-4804

文摘

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.