Abstract
Leishmaniases are a group of diseases caused by more than 20 species of the trypanosomatid parasite Leishmania, which affects 12 million people in 98 countries, and one billion are at risk of infection. There are different clinical forms, of which visceral leishmaniasis (VL) is the most aggressive. An increase in VL cases has been observed in the southern cone of Latin America. In Uruguay, it was detected in dogs for the first time in 2015, in the countryside. Therefore, there is an imminent need to develop new therapies for the treatment of leishmaniasis. With this objective, we evaluated the activity of a series of 50 compounds in vitro against Leishmania infantum, Leishmania amazonensis, and Trypanosoma brucei. Seventeen compounds from our chemical collection with good anti-trypanosomatid activity were found, with IC50 values in the range of 90 nM - 25 µM and selectivity greater than 10 concerning IC50 in murine macrophages. The selectivity of these active compounds was better than that of the reference drugs: glucantime and miltefosine. Also, using the Pathogen box chemical collection, we discovered five hits to be used in drug design and development. In vivo toxicity studies and proof of concept were also carried out in the murine model of the cutaneous form of the disease. Three of the evaluated compounds were active over the in vivo murine model of infection with 100% survival of infected animals. These results encourage us to continue the development of these molecules as anti-leishmanicidal agents.
Highlights
Cintya Perdomo a, Elena Aguilera b, Ileana Corvo a, Paula Faral-Tello c, Elva Serna d, Carlos Robello c, e, Shane R
Canine Leishmaniasis have not : A robust diagnostic method, A efficient vaccine A efficient drug The control of the vector is not easy, it cannot be controlled by insecticides
A dog culling strategy is not supportable along the time for several reasons: 1) no reliable body of scientific evidence supports the effectiveness for disease control, 2) alternative reservoir hosts may play a role in maintaining the life cycle of L. infantum, like foxes, hares, armadillos, wild boars, cats and rabbits
Summary
Canine Leishmaniasis have not : A robust diagnostic method, A efficient vaccine A efficient drug The control of the vector is not easy, it cannot be controlled by insecticides. It is a zoonotic disease, when the first case of canine leishmaniasis arrive, few years later arrives the human cases. The use of dog culling as a strategy to reduce the incidence of Visceral Leishmaniasis in humans cannot be justified and should no longer be used it is successfully used for outbreak controls in short terms of time
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