Infections by protozoans of the genus Leishmania are the major worldwide health problem, with high endemicity in developing countries. The drugs of choice for the treatment of leishmaniasis are the pentavalent antimonials, which exert renal and cardiac toxicity. Thus, there is a strong need for safer and more effective treatments against leishmaniasis. The present study was designated to evaluate, by a bioguided assay, the leishmanicidal activity of extracts (hexane, ethyl-acetate and ethanolic) and molecules both obtained by means of extraction from pericarps of Garcinia brasiliensis fruits. The hexane extract presented the best activity on the extracellular (promastigotes) and intracellular (amastigotes) forms of Leishmania (L.) amazonensis, when compared to the other extracts. Based on these findings, this extract was fractionated by silica gel column chromatography, affording nine fractions then resulting in three purified prenylated benzophenones - 7-epi-clusianone (1), garciniaphenone (2) and guttiferone-a (3). They showed significant activity on Leishmania (L.) amazonensis, and little toxicity for mammalian cells. Structure-activity relationships were evaluated showing that the IC(50) value displayed is dependent of prenyl groups and phenolic hydroxyls number, and inversely proportional to the hydrophobicity. Our results are promising, showing that these compounds are biologically active on Leishmania (L.) amazonensis.

No abstract

No abstract

The 70 kDa heat shock protein (HSP70) is a molecular chaperone that assists the parasite Leishmania in returning to homeostasis after being subjected to different types of stress during its life cycle. In the present study, we evaluated the effects of HSP70 transfection of L. amazonensis promastigotes (pTEX-HSP70) in terms of morphology, resistance, infectivity and mitochondrial bioenergetics. The pTEX-HSP70 promastigotes showed no ultrastructural morphological changes compared to control parasites. Interestingly, the pTEX-HSP70 promastigotes are resistant to heat shock, H2O2-induced oxidative stress and hyperbaric environments. Regarding the bioenergetics parameters, the pTEX-HSP70 parasites had higher respiratory rates and released less H2O2 than the control parasites. Nevertheless, the infectivity capacity of the parasites did not change, as verified by the infection of murine peritoneal macrophages and human macrophages, as well as the infection of BALB/c mice. Together, these results indicate that the overexpression of HSP70 protects L. amazonensis from stress, but does not interfere with its infective capacity.

No abstract