The antifungal compound butenafine eliminates promastigote and amastigote forms of Leishmania (Leishmania) amazonensis and Leishmania (Viannia) braziliensis

被引:14
作者
Bezerra-Souza, Adriana [1 ]
Yamamoto, Eduardo S. [1 ]
Laurenti, Marcia D. [1 ]
Ribeiro, Susan P. [2 ,3 ]
Passero, Luiz Felipe D. [4 ]
机构
[1] Univ Sao Paulo, Sch Med, Lab Pathol Infect Dis LIM 50, Ave Dr Arnaldo 455, BR-01246903 Sao Paulo, SP, Brazil
[2] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA
[3] Univ Sao Paulo, Sch Med, Div Clin Immunol & Allergy, LIM60, Sao Paulo, Brazil
[4] Univ Estadual Paulista Julio Mesquita Filho UNESP, Sao Vicente Unit, Paulista Coastal Campus, BR-11330900 Sao Vicente, SP, Brazil
基金
巴西圣保罗研究基金会;
关键词
Leishmania (Leishmania) amazonensis; Leishmania (Viannia) braziliensis; Butenafine; Antileishmanial agent; Drug repurposing; AMPHOTERICIN-B; VISCERAL LEISHMANIASIS; STEROL BIOSYNTHESIS; CELL-DEATH; MILTEFOSINE; KETOCONAZOLE; TERBINAFINE; MECHANISM; APOPTOSIS; GROWTH;
D O I
10.1016/j.parint.2016.08.003
中图分类号
R38 [医学寄生虫学]; Q [生物科学];
学科分类号
07 ; 0710 ; 09 ; 100103 ;
摘要
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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:702 / 707
页数:6
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