Autor(es):
Bezerra-Souza, Adriana ; Yamamoto, Eduardo S. ; Laurenti, Márcia D. ; Ribeiro, Susan P. ; Passero, Luiz Felipe D. [UNESP]
Data: 2018
Identificador Persistente: http://hdl.handle.net/11449/173544
Origem: Oasisbr
Assunto(s): Antileishmanial agent; Butenafine; Drug repurposing; Leishmania (Leishmania) amazonensis; Leishmania (Viannia) braziliensis
Descrição
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
The production of ergosterol lipid, important for the Leishmania membrane homeostasis, involves different enzymes. This pathway can be blocked to azoles and allylamines drugs, such as Butenafine. The aim of the present work was to evaluate the anti-leishmanicidal activity of this drug in 2 major species of Leishmania responsible for causing the American tegumentar leishmaniasis (L. (L.) amazonensis and L. (V.) braziliensis). Butenafine eliminated promastigote forms of L. amazonensis and L. braziliensis with efficacy similar to miltefosine, a standard anti-leishmania drug. In addition, butenafine induced alterations in promastigote forms of L. amazonensis that resemble programmed cell death. Butenafine as well as miltefosine presented mild toxicity in peritoneal macrophages, however, butenafine was more effective to eliminate intracellular amastigotes of both L. amazonensis and L. braziliensis, and this effect was not associated with elevated levels of nitric oxide or hydrogen peroxide. Taken together, data presented herein suggests that butenafine can be considered as a prototype drug able to eliminate L. amazonensis and L. braziliensis, etiological agents of anergic diffuse and mucocutaneous leishmaniasis, respectively.
Laboratory of Pathology of Infectious Diseases (LIM-50) Medical School University of São Paulo, Avenida Dr. Arnaldo 455
Case Western Reserve University Pathology Department
Division of Clinical Immunology and Allergy LIM60 University of Sao Paulo School of Medicine
São Vicente Unit Paulista Coastal Campus Universidade Estadual Paulista Júlio de Mesquita Filho (UNESP), Praça Infante Dom Henrique, s/n
São Vicente Unit Paulista Coastal Campus Universidade Estadual Paulista Júlio de Mesquita Filho (UNESP), Praça Infante Dom Henrique, s/n
FAPESP: 2015/18746-4