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The leishmanicidal potential of the antifungal drug Butenafine

Grant number: 15/18746-4
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): December 01, 2015
Effective date (End): November 30, 2016
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Luiz Felipe Domingues Passero
Grantee:Adriana Bezerra de Souza
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Leishmaniases are diseases caused by parasitic protozoa that infect humans, and are caused by different species belonging to Leishmania genus. The disease can be characterized by different clinical forms, depending upon of the species, and the relation between host and parasite. Leishmaniases occur in 98 countries, in five continents; therefore, it is a global concern. Even with a huge medical-epidemiological significance, the treatment is based on the Antimonials and Amphotericin B. These drugs possess serious side effects to patients, leading the therapy abandon. Therefore, new therapeutics for leishmaniases are necessary and urgent to be developed. The main goal of this project is to evaluate the leishmanicidal potential of the antifungal drug Butenafine against L. (L.) amazonensis, L. (V.) braziliensis e L. (L.) infantum parasites. Butenafine will be commercially acquired, and different concentration will be evaluated against promastigote forms of listed species. Cytotoxic potential as well as nitric oxide levels will be evaluated in J774 macrophages exposed to Butenafine. J774 macrophages will be infected by Leishmania sp. and the potential of Butanafine will be evaluated during the relation host cell and parasite, and drug potential will be expressed through Infection Index. Nitric oxide production will be evaluated in the culture of Butenafinetreated infected macrophages. Miltefosine and/or Amphotericin B will be used as standard drug in all experiments. It is well established that Butenafine inhibits squalene synthase enzyme, a pivotal enzyme to the conversion of fungal and leishmanial ergosterol, thus, it is believed that this compound are able to interfere with the viability of this parasitic genus.

Scientific publications
(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)
BEZERRA-SOUZA, ADRIANA; YAMAMOTO, EDUARDO S.; LAURENTI, MARCIA D.; RIBEIRO, SUSAN P.; PASSERO, LUIZ FELIPE D. The antifungal compound butenafine eliminates promastigote and amastigote forms of Leishmania (Leishmania) amazonensis and Leishmania (Viannia) braziliensis. Parasitology International, v. 65, n. 6, A, p. 702-707, DEC 2016. Web of Science Citations: 5.

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