title: The antifungal compound butenafine eliminates promastigote and amastigote forms of Leishmania (Leishmania) amazonensis and Leishmania (Viannia) braziliensis.
abstract: 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.
authors.affiliation: Laboratory of Pathology of Infectious Diseases (LIM-50), Medical School, University of São Paulo, Avenida Dr. Arnaldo 455, 01246903 Cerqueira César, SP, Brazil.
authors.forename: Adriana
authors.initials: A
authors.lastname: Bezerra-Souza
authors.affiliation: Laboratory of Pathology of Infectious Diseases (LIM-50), Medical School, University of São Paulo, Avenida Dr. Arnaldo 455, 01246903 Cerqueira César, SP, Brazil.
authors.forename: Eduardo S
authors.initials: ES
authors.lastname: Yamamoto
authors.affiliation: Laboratory of Pathology of Infectious Diseases (LIM-50), Medical School, University of São Paulo, Avenida Dr. Arnaldo 455, 01246903 Cerqueira César, SP, Brazil.
authors.forename: Márcia D
authors.initials: MD
authors.lastname: Laurenti
authors.affiliation: Case Western Reserve University, Pathology Department, Cleveland, USA; Division of Clinical Immunology and Allergy, LIM60, University of Sao Paulo School of Medicine, Sao Paulo, Brazil.
authors.forename: Susan P
authors.initials: SP
authors.lastname: Ribeiro
authors.affiliation: São Vicente Unit, Paulista Coastal Campus, Universidade Estadual Paulista Júlio de Mesquita Filho (UNESP), Praça Infante Dom Henrique, s/n, 11330-900 São Vicente, SP, Brazil. Electronic address: felipepassero@clp.unesp.br.
authors.forename: Luiz Felipe D
authors.initials: LF
authors.lastname: Passero
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use*; D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D001596:Benzylamines / Q000627:therapeutic use*; D058492:Drug Repositioning; D005260:Female; D007892:Leishmania braziliensis / Q000145:classification / Q000187:drug effects*; D016774:Leishmaniasis, Diffuse Cutaneous / Q000188:drug therapy* / Q000469:parasitology; D007897:Leishmaniasis, Mucocutaneous / Q000188:drug therapy* / Q000469:parasitology; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009281:Naphthalenes / Q000627:therapeutic use*; D021261:Parasitic Sensitivity Tests; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000935:Antifungal Agents; D000981:Antiprotozoal Agents; D001596:Benzylamines; D009281:Naphthalenes; D010767:Phosphorylcholine; C039128:miltefosine; C067594:butenafine
keywords: Antileishmanial agent; Butenafine; Drug repurposing; Leishmania (Leishmania) amazonensis; Leishmania (Viannia) braziliensis