Chemotherapeutic Potential of 17-AAG against Cutaneous Leishmaniasis Caused by Leishmania (Viannia) braziliensis.
In: PLoS Neglected Tropical Diseases, Jg. 8 (2014-10-01), Heft 10, S. 1-9
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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 dose-dependent 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 (O −2 ) or inflammatory mediators such as TNF-α, 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. [ABSTRACT FROM AUTHOR]
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Chemotherapeutic Potential of 17-AAG against Cutaneous Leishmaniasis Caused by Leishmania (Viannia) braziliensis.
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Autor/in / Beteiligte Person: | Santos, Diego M. ; Petersen, Antonio L. O. A. ; Celes, Fabiana S. ; Borges, Valeria M. ; Veras, Patricia S. T. ; de Oliveira, Camila I. |
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Zeitschrift: | PLoS Neglected Tropical Diseases, Jg. 8 (2014-10-01), Heft 10, S. 1-9 |
Veröffentlichung: | 2014 |
Medientyp: | academicJournal |
ISSN: | 1935-2727 (print) |
DOI: | 10.1371/journal.pntd.0003275 |
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