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In vitro antileishmanial activity of ravuconazole, a triazole antifungal drug, as a potential treatment for leishmaniasis.
Teixeira de Macedo Silva, Sara; Visbal, Gonzalo; Lima Prado Godinho, Joseane; Urbina, Julio A; de Souza, Wanderley; Cola Fernandes Rodrigues, Juliany.
Afiliação
  • Teixeira de Macedo Silva S; Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
  • Visbal G; Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem, Rio de Janeiro, Brazil.
  • Lima Prado Godinho J; Instituto Nacional de Metrologia, Qualidade e Tecnologia, Rio de Janeiro, Brazil.
  • Urbina JA; Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
  • de Souza W; Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem, Rio de Janeiro, Brazil.
  • Cola Fernandes Rodrigues J; Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela.
J Antimicrob Chemother ; 73(9): 2360-2373, 2018 09 01.
Article em En | MEDLINE | ID: mdl-29982734
Objectives: Leishmaniasis, one of the most significant neglected diseases around the world, is caused by protozoan parasites of the Leishmania genus. Nowadays, the available aetiological treatments for leishmaniasis have variable effectiveness and several problems such as serious side effects, toxicity, high cost and an increasing number of resistance cases. Thus, there is an urgent need for safe, oral and cost-effective drugs for leishmaniases. Previously, our group has shown the effect of the ergosterol biosynthesis inhibitors on Leishmania amazonensis. Herein, we showed the effect of ravuconazole against L. amazonensis; ravuconazole is a second-generation triazole antifungal drug that has good bioavailability after oral administration and a long terminal half-life in humans, a broad activity spectrum, high effectiveness in treatment of mycosis and negligible side effects. Methods: Several methodologies were used: cell culture, fluorescence and electron microscopy, high-resolution capillary GC coupled with MS, fluorimetry and flow cytometry. Results: Our results showed that ravuconazole was able to inhibit the proliferation of L. amazonensis promastigotes and intracellular amastigotes in vitro, with single-digit to sub-micromolar IC50 values, causing several alterations in the morphology, ultrastructure, cell viability and physiology of the parasites. The mitochondrion was significantly affected by the treatment, resulting in a collapse of the mitochondrial transmembrane potential that consequently led to inhibition of ATP production, combined with an increase in reactive oxygen species and mitochondrial superoxide production; by transmission electron microscopy, the organelle displayed a completely altered ultrastructure. The treatment changed the lipid profile, showing a profound depletion of the 14-desmethyl endogenous sterol pool. Conclusions: These results suggest that ravuconazole could be an alternative option for the treatment of leishmaniasis.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tiazóis / Triazóis / Leishmania mexicana / Reposicionamento de Medicamentos / Antiprotozoários Idioma: En Revista: J Antimicrob Chemother Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tiazóis / Triazóis / Leishmania mexicana / Reposicionamento de Medicamentos / Antiprotozoários Idioma: En Revista: J Antimicrob Chemother Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido