Ruthenium complexes endowed with potent anti-Trypanosoma cruzi

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• 作者：Claudio Luis Donnici ; Maria Helena Araú ; jo ; Henrique S. Oliveira ; Diogo Rodrigo Magalhã ; es Moreira ; Valé ; ria R. Alves Pereira ; Marina de Assis Souza ; Maria Carolina Accioly Brelaz de Castr
• 关键词：Trypanosoma cruzi ; Metal complexes ; Ruthenium ; Thiazole ; Hydrazone ; DNA interaction
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2009
• 出版时间：15 July 2009
• 年：2009
• 卷：17
• 期：14
• 页码：5038-5043
• 全文大小：276 K

文摘

Although effective against epimastigotes (proliferative form) and of low cytotoxicity in mammals, the aryl-4-oxothiazolylhydrazones (ATZ) display only limited activity against trypomastigotes (bloodstream form) of Trypanosoma cruzi. Considering the metal complexation approach with bioactive ligands as one possible strategy for improving the biological efficacy of ATZ, a set of eight new ruthenium–ATZ complexes (RuCl₂ATZCOD, COD is 1,5-cyclooctadiene) were prepared, chemically and biologically characterized, including in vitro assays against epimastigotes and trypomastigote forms of the parasite and also assessment of cytotoxicity in mammals. Two of these complexes presented antitrypanosomal activity at non-cytotoxic concentrations on mammalian cells and of higher potency than its metal–free ligands, while the metallic precursor [RuCl₂COD(MeCN)₂] showed only moderate antitrypanosomal activity. Comparative analysis between the ruthenium complexes and metal–free ligands demonstrated the usefulness of this approach, with the establishment of new SAR data. Additional pharmacological tests, including a DNA bond assay, gave rise to the proposal of a single preliminary explanation for the molecular origin of the bioactivity.