Platinum(II) metal complexes as potential anti-Trypanosoma cruzi agents

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• 作者：Marisol Vieites ; Lucí ; a Otero ; Diego Santos ; Jeannette Toloza ; Roberto Figueroa ; Ester Norambuena ; Claudio Olea-Azar ; Gabriela Aguirre ; Hugo Cerecetto ; Mercedes Gonzá ; lez ; Antonio Morello ; Jua
• 关键词：Chagas&#x2019 ; disease ; Platinum ; 5-Nitrofuryl containing thiosemicarbazones ; Free radical production ; N ; S ligands
• 刊名：Journal of Inorganic Biochemistry
• 出版年：2008
• 期刊代码：53_01620134
• 类别：ch
• 出版时间：May 2008
• 卷：102
• 期：5-6
• 页码：1033-1043
• 文件大小：243 K

摘要

In the search for new therapeutic tools against Chagas’ disease (American Trypanosomiasis) two series of new platinum(II) complexes with bioactive 5-nitrofuryl containing thiosemicarbazones as ligands were synthesized, characterized and in vitro evaluated. Most of the complexes showed IC₅₀ values in the μM range against two different strains of Trypanosoma cruzi, causative agent of the disease, being as active as the anti-trypanosomal drug Nifurtimox. In particular, the coordination of L3 (4-ethyl-1-(5-nitrofurfurylidene)thiosemicarbazide) to Pt(II) forming [Pt(L3)₂] lead to almost a five-fold activity increase in respect to the free ligand. Trying to get an insight into the trypanocidal mechanism of action of these compounds, DNA and redox metabolism (intra-parasite free radical production) were evaluated as potential parasite targets. Results suggest that the complexes could inhibit parasite growth through a dual mechanism of action involving production of toxic free radicals by bioreduction and DNA interaction.