In vivo and in vitro auranofin activity against Trypanosoma cruzi: Possible new uses for an old drug

被引:27
|
作者
Alves da Silva, Marco Tulio [1 ]
Silva-Jardim, Izaltina [1 ,4 ]
Portapilla, Gisele Bulhoes [1 ,5 ]
Alvares de Lima, Gustavo Machado [1 ,6 ]
Costa, Fernanda Cristina [1 ,2 ,7 ]
Anibal, Fernanda de Freitas [3 ]
Thiemann, Otavio Henrique [1 ,2 ]
机构
[1] Univ Sao Paulo, Inst Fis Sao Carlos, Caixa Postal 369, BR-13560590 Sao Carlos, SP, Brazil
[2] Univ Fed Sao Carlos, Dept Genet & Evolucao, BR-13560 Sao Carlos, SP, Brazil
[3] Univ Fed Sao Carlos, Dept Morfol & Patol, Caixa Postal 676, BR-13565905 Sao Carlos, SP, Brazil
[4] Univ Estadual Santa Cruz, Dept Ciencias Biol, Campus Soane Nazare de Andrade, BR-45662900 Ilheus, BA, Brazil
[5] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Ave Cafe,S-N Monte alegre, BR-14040903 Ribeirao Preto, SP, Brazil
[6] Univ Sao Paulo, Inst Fis Sao Carlos, LQMC, Caixa Postal 369, BR-13560590 Sao Carlos, SP, Brazil
[7] Ctr Nacl Pesquisa Energia & Mat, Lab Nacl Biociencias, Rua Giuseppe Maximo Scolfaro 10-000, BR-13083970 Campinas, SP, Brazil
基金
巴西圣保罗研究基金会;
关键词
Trypanosoma cruzi; Chemotherapy; Auranofin; THIOREDOXIN-GLUTATHIONE-REDUCTASE; RHEUMATOID-ARTHRITIS; APOPTOSIS;
D O I
10.1016/j.exppara.2015.05.012
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
Chagas disease, Sleeping Sickness, Nagana and Leishmaniasis are serious infections caused by protozoa of the order Kinetoplastidae. They were described over a century ago by seminal work of different physician-researchers and, despite the initial discoveries, few drugs have been made available for the treatment of these infections. The drugs available present serious efficacy and toxicity problems. Moreover, the emergence of resistant strains has rendered the development of novel chemotherapeutic strategies a priority. Auranofin is currently in use to treat rheumatoid arthritis in humans. Previous reports showed that this compound presents activity against Trypanosoma brucei and Leishmania cells. In Trypanosome cruzi cells, auranofin resulted in a more potent compound than benznidazole in vitro when tested in different DTUs. In vivo experiments, although not decreasing T cruzi parasitemia, decreases host mortality. Therefore, we propose auranofin as a potential alternative for a new chemotherapy in Chagas disease with the added advantage of already being approved for use in humans. (C) 2015 Elsevier Inc. All rights reserved.
引用
收藏
页码:189 / 193
页数:5
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