Abstract
In the search for new therapies, drug repositioning has been a successful innovation strategy and exploited by big pharmaceutical companies. Basically, it consists in finding a new use of drugs for approved drugs, which has been considered a highly favorable strategy in the current scenario of protozoosis neglected as visceral leishmaniasis (VL). Considering that Leishmaniasis is distributed in 98 countries, with 12 million infected, it has been considered one of the major parasitic diseases for WHO. Considering the increase of cases of VL in unaffected regions, the reduced therapeutic arsenal and the high toxicity of drugs, there is a need for selecting new antiparasitic agents. This proposal aims to study new therapies using in vitro and in vivo models of Leishmania (L.) infantum chagasi, using the following approaches: i) repositioning drugs- in vitro screening of approved drugs and available in the market for different therapeutic purposes such as antipsychotics, antagonists of histamine receptors, benzodiazepines, among others, ii) study of the mechanism of action- cellular alterations of Leishmania will be evaluated by spectrofluorimetric techniques, flow cytometry, confocal microscopy and transmission electron microscopy in order study apoptosis, alteration of the permeability of the plasma membrane, disturbance of mitochondrial membrane potential, generation of reactive oxygen species (ROS), etc., iii) drug delivery systems (liposomes) - evaluation of the effectiveness of drugs, free or included into liposomes, using experimental infected hamsters, and quantifying treatment by real-time PCR. The discovery of approved drugs in clinical use for other diseases, as well as the exploration of its mechanisms of action in the parasite, could contribute to the selection of more effective therapies, reducing costs and time for the search of new drugs for neglected diseases. (AU)
Scientific publications
(13)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
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