| Author | Santos, Diego Moura | |
| Author | Petersen, Antonio Luis de Oliveira Almeida | |
| Author | Celes, Fabiana Santana | |
| Author | Borges, Valeria de Matos | |
| Author | Veras, Patrícia Sampaio Tavares | |
| Author | Oliveira, Camila Indiani de | |
| Access date | 2014-11-12T18:52:56Z | |
| Available date | 2014-11-12T18:52:56Z | |
| Document date | 2014 | |
| Citation | SANTOS, D. M. et al. Chemotherapeutic Potential of 17-AAG againstCutaneous Leishmaniasis caused by Leishmania (Viannia) braziliensis. PLoS Neglected Tropical Diseases, v. 8, n. 10, p. e3275, 2014. | pt_BR |
| ISSN | 1935-2727 | |
| URI | https://www.arca.fiocruz.br/handle/icict/8817 | |
| Language | eng | pt_BR |
| Publisher | Public Library of Science | pt_BR |
| Rights | open access | pt_BR |
| Subject in Portuguese | Leishmaniose | pt_BR |
| Subject in Portuguese | Leishmaniose cutânea | pt_BR |
| Subject in Portuguese | Leishmaniose Tegumentar | pt_BR |
| Subject in Portuguese | Leishmania (Viannia) braziliensis | pt_BR |
| Subject in Portuguese | Saúde pública | pt_BR |
| Title | Chemotherapeutic Potential of 17-AAG againstCutaneous Leishmaniasis caused by Leishmania (Viannia) braziliensis | pt_BR |
| Type | Article | pt_BR |
| DOI | 10.1371/journal.pntd.0003275 | |
| Abstract | Background: Leishmaniasis remains a worldwide public health problem. The limited therapeutic options, drug toxicity and
reports of resistance, reinforce the need for the development of new treatment options. Previously, we showed that 17-
(allylamino)-17-demethoxygeldanamycin (17-AAG), a Heat Shock Protein 90 (HSP90)-specific inhibitor, reduces L. (L.)
amazonensis infection in vitro. Herein, we expand the current knowledge on the leishmanicidal activity of 17-AAG against
cutaneous leishmaniasis, employing an experimental model of infection with L. (V.) braziliensis.
Methodology/Principal findings: Exposure of axenic L. (V.) braziliensis promastigotes to 17-AAG resulted in direct dosedependent
parasite killing. These results were extended to L. (V.) braziliensis-infected macrophages, an effect that was
dissociated from the production of nitric oxide (NO), superoxide (O22) or inflammatory mediators such as TNF-a, IL-6 and
MCP-1. The leishmanicidal effect was then demonstrated in vivo, employing BALB/c mice infected with L. braziliensis. In this
model, 17-AAG treatment resulted in smaller skin lesions and parasite counts were also significantly reduced. Lastly, 17-AAG
showed a similar effect to amphotericin B regarding the ability to reduce parasite viability.
Conclusion/Significance: 17-AAG effectively inhibited the growth of L. braziliensis, both in vitro and in vivo. Given the
chronicity of L. (V.) braziliensis infection and its association with mucocutaneous leishmaniasis, 17-AAG can be envisaged as
a new chemotherapeutic alternative for cutaneous Leishmaniasis. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia de Investigação em Imunologia (iii-INCT). Salvador, BA, Brasil | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia de Investigação em Imunologia (iii-INCT). Salvador, BA, Brasil | pt_BR |
