A New Promising Application for Highly Cytotoxic Metal Compounds: 畏6-Areneruthenium(II) Phosphite Complexes for the Treatment of Alveolar Echinococcosis

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• 作者：Tatiana K眉ster ; Nadine Lense ; Fabienne Barna ; Andrew Hemphill ; Markus K. Kindermann ; Joachim W. Heinicke ; Carsten A. Vock
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：May 10, 2012
• 年：2012
• 卷：55
• 期：9
• 页码：4178-4188
• 全文大小：516K
• 年卷期：v.55,no.9(May 10, 2012)
• ISSN：1520-4804

文摘

Two series of 畏⁶-areneruthenium(II) phosphite complexes were prepared, characterized, and evaluated in vitro for their toxic potential against Echinococcus multilocularis metacestodes. Neutral complexes of general formula [(畏⁶-p-cymene)RuCl₂{P(OR)₃}] (R = Et, ⁱPr, Ph) with two easily exchangable chloride ligands showed only minor toxicity, whereas the substitution of these moieties against a 尾-diketonate (2,2,6,6-tetramethylheptanedionate) ligand led to hydrolytically stable complex salts of type [(畏⁶-p-cymene)Ru(尾-diketonate){P(OR)₃}][BF₄] (R = Et, ⁱPr, Ph) with comparable in vitro toxicity (50% PGI release at c = 1.4 鈥?4.7 渭M) to the reference drug nitazoxanide (50% PGI release at c = 1.2 渭M). In addition, the latter complexes were highly toxic against rat hepatoma cells (IC₅₀ = 0.40鈥?.0 渭M) and less toxic against human foreskin fibroblasts (IC₅₀ = 1.1鈥?.9 渭M) and Vero cells (IC₅₀ = 1.2鈥?.9 渭M). The measured cytotoxicities against mammalian cells are, to the best of our knowledge, among the highest ever observed for ruthenium-based complexes. In conclusion, complex salts of type [(畏⁶-p-cymene)Ru(尾-diketonate){P(OR)₃}][BF₄] might be interesting candidates for further development toward anthelmintic drugs and/or highly cytotoxic metal compounds.