Abstract
BackgroundAmong the tropical parasitic diseases, those caused by protozoans are considered a challenge to public health, being represented by leishmaniasis and Chagas disease. In view of the low effectiveness and toxicity of the current therapy, animal venoms such as amphibian secretions have been used as a promising source of new drug prototypes. The present work aimed to achieve bioguided fractionation of metabolites present in a cutaneous secretion of the caecilian Siphonops annulatus (Amphibia: Gymnophiona: Siphonopidae) with antileishmanial and antitrypanosomal activity.MethodsThrough liquid-liquid partition and chromatographic techniques, the secretion was fractionated using bioguided assays. The 50% inhibitory concentration (IC50) of the main fraction (SaFr1) was studied against Leishmania (L.) infantum promastigotes and intracellular amastigotes, trypomastigotes of Trypanosoma cruzi and mammalian cells; viability was detected by the colorimetric MTT assay. By using a spectrofluorimetric assay with the probe SYTOX® Green and transmission electron microscopy (TEM), we also investigated the potential damage caused by SaFr1 in the plasma membrane and mitochondria of Leishmania.ResultsThe bioguided assay enabled isolation of a highly purified fraction (SaFr1) with an IC50 of 0.065 μg/mL against promastigotes and 2.75 μg/mL against trypomastigotes. Due to its high toxicity to peritoneal macrophages, SaFr1 showed no selectivity towards the intracellular forms of Leishmania. Ultrastructural studies with Leishmania demonstrated severe mitochondrial damage and the formation of large cytoplasmic vacuoles, leading to the parasite’s death within a few hours. Nevertheless, it caused no alteration in the plasma membrane permeability as detected by the fluorescent probe and TEM.ConclusionsThe present study demonstrated for the first time the antiparasitic activity of the skin secretion of the caecilian S. annulatus against Leishmania and T. cruzi, confirming that skin secretions of these amphibians, similarly to those of anurans and salamanders, are also potential tools for the development of new drug candidates against neglected diseases.
Highlights
Among the tropical parasitic diseases, those caused by protozoans are considered a challenge to public health, being represented by leishmaniasis and Chagas disease
Among the natural toxins used as important tools in the development of new drugs, amphibian secretions represent a rich source of metabolites, providing potential candidates for drug design studies
By using bioguided fractionation, we investigated the antiprotozoal activity of metabolites isolated from the cutaneous secretion of the Brazilian caecilian Siphonops annulatus (Amphibia: Gymnophiona: Siphonopidae) using liquid-liquid partition and reversedphase ultra-performance liquid chromatography, coupled to a photodiode array detector (RP-UPLC-PDA)
Summary
Among the tropical parasitic diseases, those caused by protozoans are considered a challenge to public health, being represented by leishmaniasis and Chagas disease. In view of the low effectiveness and toxicity of the current therapy, animal venoms such as amphibian secretions have been used as a promising source of new drug prototypes. American trypanosomiasis or Chagas disease has been considered among the most neglected afflictions in several underdeveloped and developing countries, and affects about 28 million people in Latin America [3]. It is caused by the flagellate protozoan parasite Trypanosoma cruzi and is transmitted to humans by triatomine insects primarily during insect feeding, or by blood transfusion and congenital transmission [4]. There is an essential need for the discovery of new drug entities, using animal toxins as a source [6,7]
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