|Support type:||Scholarships in Brazil - Doctorate|
|Effective date (Start):||February 01, 2012|
|Effective date (End):||October 31, 2015|
|Field of knowledge:||Biological Sciences - Parasitology - Protozoology of Parasites|
|Principal Investigator:||Silvia Reni Bortolin Uliana|
|Grantee:||Cristiana de Melo Trinconi Tronco|
|Home Institution:||Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil|
Leishmaniasis is a disease with a wide clinical spectrum caused by more than 20 species of protozoa of the genus Leishmania. The disease is distributed worldwide and its incidence has increased considerably in recent decades. Current treatment schemes present many problems with responses that are often unpredictable and unsatisfactory. In addition, some strains of Leishmania have shown resistance to classical drugs, leading many authors to propose the use of combination therapies. Studies in our laboratory demonstrated the leishmanicidal activity of the anticancer compound tamoxifen. We found that this drug is active against several species of Leishmania in vitro and in vivo both by parenteral and topical routes. We also observed that tamoxifen causes changes in the biosynthesis of sphingolipids in Leishmania. The main changes observed are related to the synthesis of ceramide, acylated ceramide, glucosylceramide and inositolphosphorylceramide. Consequently, the objectives of this project are: i) to evaluate the effectiveness of tamoxifen in combination with drugs currently used in the therapy of leishmaniasis in vitro and in vivo, and ii) to characterize the effect of tamoxifen on the biosynthesis of sphingolipids in Leishmania, with particular focus on the activity of ceramidase and glucosylceramide synthase, as well as in the de novo synthesis of inositol and its transport in treated cells.