In this review, we present the potential use of the heterocyclic oxadiazole rings in the design and synthesis of new drugs to treat parasitic infections. We intend to compare herein all the four isomeric forms of oxadiazole rings as well as discuss the differences and similarities between them. In addition, we discuss aspects on their reactivity that justify the great importance of both 1,2,4-and 1,3,4-oxadiazoles isomers when compared with their other two isomers. Although some oxadiazole isomers satisfy Hückel's rule, there are differences concerning their aromaticity, which have a great impact on the possible interactions of the oxadiazole ring with biological receptors. The set of works selected from the literature and discussed herein points out the oxadiazole core as an important and versatile scaffold in the development of new chemical entities potentially useful as antiparasitic drugs.
In a previous work, we have investigated the effects of piperine and several of its chemical derivatives on the proliferation of the protozoan parasite Trypanosoma cruzi. It was observed that natural piperine is more active against intracellular amastigotes than axenically grown epimastigotes with IC50 values of 4.91 and 7.36 microM, respectively. Despite its superior trypanocidal activity against the intracellular amastigotes, here, we show that piperine did not enhance microbiocidal characteristics of murine peritoneal macrophages (Mø) based on nitric oxide production. As shown by light and electron microscopy analysis, epimastigotes treated with sublethal concentrations of piperine presented a reversible cell cycle arrestment and become round shaped, with swelling of the mitochondrion matrix and intense intracellular vacuolization with structures displaying complex membrane invaginations. Similar to the effects of exposing epimastigotes to the antitumor and microtubule stabilizer taxol, multiplication of cell organelles such as the flagellum, kinetoplast, and nucleus occurred, but division into daughter cells was impaired. Unlike the effects caused by the anti-microtubular vinca alkaloids vincristine and vinblastine, which also induce cytokinesis arrestment in T. cruzi epimastigotes, piperine did not induce the formation of giant multinucleated cells. The data reinforce the selectivity of the mechanisms of action of piperine against T. cruzi.
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