New imidazolidine derivatives as anti-Trypanosoma cruzi agents: structure-activity relationships

作者：dos Santos Gomes Fabiana Oliveira; Lagos de Melo Cristiane Moutinho; Peixoto Christina Alves; Alves de Lima Maria do Carmo; Galdino Suely Lins; Alves Pereira Valeria Rego; Pitta Ivan da Rocha

来源：Parasitology Research, 2012, 111(6): 2361-2366.

DOI：10.1007/s00436-012-3091-7

Imidazolidine derivatives are key components for the development of bioactive compounds for the treatment of many diseases, especially Chagas. In fact, others studies showed that the imidazolidine-2,4-dione has stood out by presenting a wide spectrum of pharmacological activities including anticonvulsants, antiarrhythmic, and antiparasitic. In the present study, we investigated the morphological alterations induced by imidazolidine derivates LPSF/NN-52 and LPSF/NN-100 on trypomastigotes forms of Trypanosoma cruzi through ultrastructural analysis by electron microscopy. Many concentrations were used to measure the antiparasitic propriety promoted by imidazolidine derivatives, and our study indicates that parasites treated with 13 mu g mL(-1) of the imidazolidine derivates for 24 h revealed severe damage to the parasite%26apos;s mitochondrial complex. Beyond that, also observed in treated parasites were the following: myelin bodies, enlargement of cytoplasm vacuole, fragmentation of endoplasmic reticulum, and some treated samples clearly showed signs of necrosis. To confirm the ultrastructural results, some assays were performed for knowledge cellular death induction promoted by imidazolidine derivates against immune spleen cells. The induction of the necrotic process through derivatives LPSF/NN-52 and LPSF/NN-100 showed similar results in relation to nifurtimox and benznidazole. In the last assays, it was demonstrated that NN-100 was efficient against epimastigotes and trypomastigotes forms and these results reinforce the mechanisms of action of both new imidazolidine derivatives against T. cruzi.

• 出版日期2012-12