Chemotherapeutic Potential of 17-AAG against Cutaneous Leishmaniasis Caused by Leishmania (Viannia) braziliensis

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. © 2014 santos et al.