Atividade da punicalagina em leveduras do complexo Cryptococcus neoformans e de espécies de Candida
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2017-09-12
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Universidade Federal de Goiás
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Introduction: the high incidence and mortality rate due to fungal infections arouse interest
in the search for more effective and less toxic drugs for the treatment of these infections.
Medicinal plants represent a promising source of discovery of antifungal agents. Among the
medicinal plants, Lafoensia pacari A. St.-Hil (Lythraceae), plant of the cerrado, stands out for
having medicinal properties popularly known in Brazil. Punicalagina, a secondary metabolite
extracted from L. pacari leaf, has proven biological activities. Objective: in this work the
biological activity of punicalagin on yeasts belonging to the Cryptococcus neoformans species
complex and Candida species was evaluated. Methods: the in vitro susceptibility of the yeast
to the compound punicalagin was verified using the broth microdilution method. The possible
mechanism of action was verified by different methods such as: ergosterol assay of the fungal
cell membrane, by morphological and ultrastructural analyzes of the yeasts, by flow
cytometry (cell cycle, cytoplasmic membrane injury, reactive oxygen species production and
loss of the mitochondrial membrane potential). The in vitro cytotoxicity of punicalagin was
verified using Balb/c 3T3 cells, A549 lung carcinoma cells and sheep erythrocytes.
Results: the punicalagin was able to inhibit yeast growth at concentrations ≤4 μg/mL with
minimum fungicidal concentration (CFM) of >256 μg/mL. The punicalagin reduced the
ergosterol synthesis of the fungal cell membrane and promoted alterations in the morphology
and the cellular arrangement of the yeasts. The action mechanism analyzed by flow cytometry
showed alteration of the cell cycle with increase of the G0/G1 phases and reduction of the
G2/M phases, interfering in the cellular division of the DNA of the fungal cells. The compound
showed low toxicity on the Balb/c cells 3T3, A549 and sheep erythrocytes. Conclusion: the
results presented by punicalagin showed that this compound presents low cytotoxicity to the
animal cells, with important antifungal activity against the yeasts of the Cryptococcus
neoformans species complex and Candida species.
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SILVA, T. C. Atividade da punicalagina em leveduras do complexo Cryptococcus neoformans e de espécies de Candida. 2017. 109 f. Tese (Doutorado em Medicina Tropical e Saúde Pública) - Universidade Federal de Goiás, Goiânia, 2017.