In vitro antileishmanial activity of ravuconazole, a triazole antifungal drug, as a potential treatment for leishmaniasis
| العنوان: | In vitro antileishmanial activity of ravuconazole, a triazole antifungal drug, as a potential treatment for leishmaniasis |
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| المؤلفون: | Wanderley de Souza, Joseane Lima Prado Godinho, Juliany Cola Fernandes Rodrigues, Sara Teixeira de Macedo Silva, Gonzalo Visbal, Julio A. Urbina |
| المصدر: | Journal of Antimicrobial Chemotherapy. 73:2360-2373 |
| بيانات النشر: | Oxford University Press (OUP), 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Microbiology (medical), Leishmania mexicana, 030106 microbiology, Antiprotozoal Agents, Triazole, Antifungal drug, Mitochondrion, Pharmacology, Ravuconazole, Mass Spectrometry, Inhibitory Concentration 50, 03 medical and health sciences, chemistry.chemical_compound, Parasitic Sensitivity Tests, medicine, Fluorometry, Pharmacology (medical), Viability assay, Amastigote, biology, Drug Repositioning, Leishmaniasis, Triazoles, Flow Cytometry, Leishmania, biology.organism_classification, medicine.disease, Microscopy, Electron, Thiazoles, Infectious Diseases, Microscopy, Fluorescence, chemistry |
| الوصف: | 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. |
| تدمد: | 1460-2091 0305-7453 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e91c9e5a659c34f589f91c3206d0d951 https://doi.org/10.1093/jac/dky229 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....e91c9e5a659c34f589f91c3206d0d951 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14602091 03057453 |
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