Effects of two 6-quinolinyl chalcones on the integrity of plasma membrane of Paracoccidioides brasiliensis
| Autor: | Patrícia Silva Cisalpino, Beatriz M. Borelli, Luciana de Carvalho Tavares, Gabriele de Matos Cardoso Perdigão, Carlos A. Rosa, Susana Johann, Nívea Pereira de Sá, Moacir Geraldo Pizzolatti, Elaine M. Souza-Fagundes, Paulo Js Barbeira, Leandro Espíndola |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cytoplasm Antifungal Agents 030106 microbiology Microbial Sensitivity Tests Paracoccidioides Microbiology 03 medical and health sciences chemistry.chemical_compound Chalcones Amphotericin B Ergosterol Drug Discovery Chlorocebus aethiops Trimethoprim Sulfamethoxazole Drug Combination medicine Animals Propidium iodide Viability assay Vero Cells Pharmacology Paracoccidioides brasiliensis biology Paracoccidioidomycosis Cell Membrane medicine.disease biology.organism_classification chemistry Potassium Efflux medicine.drug |
| Zdroj: | The Journal of antibiotics. 70(3) |
| ISSN: | 1881-1469 |
| Popis: | Paracoccidioidomycosis is the most prevalent systemic mycosis in Latin America, yet few therapeutic options exist. Our aim was to search for new compounds with high efficacy, low toxicity, shorter treatment time and affordable cost. We studied two synthetic 6-quinolinyl chalcones, 3b and 3e, to determine their effects on VERO cells, antifungal activity, survival curve, interaction with other drugs and phenotypic effects against several isolates of Paracoccidioides spp. In this study, we verified that the compounds were not toxic, exhibited superior in vitro activity compared with that shown by trimethoprim–sulfamethoxazole, and after 5 days of treatment, decreased the fungal cell viability by approximately 70%. Additionally, no interactions were observed between the tested compounds and other drugs. We also found that these compounds induced morphological changes, such as shriveling of cells, fragmentation of the plasma membrane and cytoplasmic disorganization in vitro. The changes observed by microscopy assays corroborate the observation made with propidium iodide, where the number of cells stained with the compounds was higher than that observed after amphotericin B treatment. We observed an increase in the efflux of K+ and a loss of intracellular contents in cells treated with 3b and 3e, confirming their effects on fungal membranes. However, damage to the membrane was not associated with a decrease in membrane ergosterol levels. The experimental evidences showed no direct indications of cellular wall damage caused by these compounds. Thus, these results confirm the antifungal potential of 3b and 3e against Paracoccidioides spp. with possible action on the membrane. |
| Databáze: | OpenAIRE |
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