Abstract：
In this work, two analogous coumarin-thio and semicarbazone hybrid compounds were prepared and evaluated as a potential antichagasic agents. Furthermore, palladium and platinum complexes with the thiosemicarbazone derivative as ligand (L1) were obtained in order to establish the effect of metal complexation on the antiparasitic activity. All compounds were fully characterized both in solution and in solid state including the resolution of the crystal structure of the palladium complex by X-ray diffraction methods. Unexpectedly, all experimental and theoretical characterizations in the solid state, demonstrated that the obtained palladium and platinum complexes are structurally different: [PdCl(L1)] and [PtCl2(HL1)]. All the studied compounds lower the proliferation of the amastigote form of Trypanosoma cruzi while some of them also have an effect on the trypomastigote stage. Additionally, the compounds inhibit T. cruzi release from host cells in variable extents. The Pd compound presented a remarkable profile in all the in vitro experiments, and it showed no toxicity for mammalian cells in the assayed concentrations. In this sense, in vivo experiments were performed for this compound using an acute model of Chagas disease. Results showed that the complex significantly lowered the parasite count in the mice blood with no significant toxicity.
摘要：
在这项工作中,制备了两种类似的香豆素-硫代和氨基脲杂化化合物，并将其评估为潜在的抗cha药。此外，获得了以氨基硫脲衍生物为配体（L1）的钯和铂配合物，以确定金属配合物对抗寄生虫活性的影响。所有化合物在溶液和固态中均得到充分表征，包括通过X射线衍射方法解析钯配合物的晶体结构。出乎意料的是,固态下的所有实验和理论表征，证明所获得的钯和铂配合物在结构上不同：[PdCl（L1）]和[PtCl2（HL1）]。所有研究的化合物均降低了克氏锥虫的amastigote形式的增殖，而其中一些化合物也对锥虫阶段有影响。此外,这些化合物在不同程度上抑制T.cruzi从宿主细胞的释放。Pd化合物在所有的体外实验中都表现出了显著的特征，在测定的浓度下，它对哺乳动物细胞没有毒性。在这个意义上,使用查加斯病的急性模型对该化合物进行体内实验。结果表明，该复合物显着降低了小鼠血液中的寄生虫数量，没有明显的毒性。
