Vieites Marisol, Otero Lucía, Santos Diego, Toloza Jeannette, Figueroa Roberto, Norambuena Ester, Olea-Azar Claudio, Aguirre Gabriela, Cerecetto Hugo, González Mercedes, Morello Antonio, Maya Juan Diego, Garat Beatriz, Gambino Dinorah
Cátedra de Química Inorgánica, Facultad de Química, Universidad de la República, Gral. Flores 2124, CC 1157, 11800 Montevideo, Uruguay.
J Inorg Biochem. 2008 May-Jun;102(5-6):1033-43. doi: 10.1016/j.jinorgbio.2007.12.005. Epub 2007 Dec 23.
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 muM 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.
在寻找治疗恰加斯病（美洲锥虫病）的新治疗工具的过程中，合成、表征并体外评估了两组以含生物活性5-硝基糠基的硫代半卡巴腙为配体的新型铂（II）配合物。大多数配合物对该疾病的病原体克氏锥虫的两种不同菌株显示出微摩尔范围内的IC50值，其活性与抗锥虫药物硝呋替莫相当。特别是，L3（4-乙基-1-（5-硝基糠叉基）硫代半卡巴腙）与Pt（II）配位形成[Pt（L3）2]，相对于游离配体，活性提高了近五倍。为了深入了解这些化合物的杀锥虫作用机制，对DNA和氧化还原代谢（寄生虫内自由基产生）作为潜在的寄生虫靶点进行了评估。结果表明，这些配合物可通过涉及生物还原产生有毒自由基和DNA相互作用的双重作用机制抑制寄生虫生长。
