Screening and antifungal activity of a β-carboline derivative against cryptococcus neoformans and C. gattii
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional do INPA |
Texto Completo: | https://repositorio.inpa.gov.br/handle/1/15581 |
Resumo: | Background. Cryptococcosis is a fungal disease of bad prognosis due to its pathogenicity and the toxicity of the drugs used for its treatment. The aim of this study was to investigate the medicinal potential of carbazole and β-carboline alkaloids and derivatives against Cryptococcus neoformans and C. gattii. Methods. MICs were established in accordance with the recommendations of the Clinical and Laboratory Standards Institute for alkaloids and derivatives against C. neoformans and C. gattii genotypes VNI and VGI, respectively. A single active compound was further evaluated against C. neoformans genotypes VNII, VNIII, and VNIV, C. gattii genotypes VGI, VGIII, and VGIV, Candida albicans ATCC 36232, for cytotoxicity against the MRC-5 lineage of human fibroblasts and for effects on fungal cells (cell wall, ergosterol, and leakage of nucleic acids). Results. Screening of 11 compounds revealed 8-nitroharmane as a significant inhibitor (MIC 40 μg/mL) of several C. neoformans and C. gattii genotypes. It was not toxic to fibroblasts (IC 50 > 50 μg/mL) nor did it alter fungal cell walls or the concentration of ergosterol in C. albicans or C. neoformans. It increased leakage of substances that absorb at 260 nm. Conclusions. The synthetic β-carboline 8-nitroharmane significantly inhibits pathogenic Cryptococcus species and is interesting as a lead compound towards new therapy for Cryptococcus infections. © 2019 Kátia Santana Cruz et al. |
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Cruz, Kátia SantanaLima, Emerson SilvaSilva, Marcia de Jesus Amazonas daSouza, Érica Simplício deMontoia, AndréiaPohlit, Adrian MartinSouza, João Vicente Braga de2020-05-15T00:09:40Z2020-05-15T00:09:40Z2019https://repositorio.inpa.gov.br/handle/1/1558110.1155/2019/7157845Background. Cryptococcosis is a fungal disease of bad prognosis due to its pathogenicity and the toxicity of the drugs used for its treatment. The aim of this study was to investigate the medicinal potential of carbazole and β-carboline alkaloids and derivatives against Cryptococcus neoformans and C. gattii. Methods. MICs were established in accordance with the recommendations of the Clinical and Laboratory Standards Institute for alkaloids and derivatives against C. neoformans and C. gattii genotypes VNI and VGI, respectively. A single active compound was further evaluated against C. neoformans genotypes VNII, VNIII, and VNIV, C. gattii genotypes VGI, VGIII, and VGIV, Candida albicans ATCC 36232, for cytotoxicity against the MRC-5 lineage of human fibroblasts and for effects on fungal cells (cell wall, ergosterol, and leakage of nucleic acids). Results. Screening of 11 compounds revealed 8-nitroharmane as a significant inhibitor (MIC 40 μg/mL) of several C. neoformans and C. gattii genotypes. It was not toxic to fibroblasts (IC 50 > 50 μg/mL) nor did it alter fungal cell walls or the concentration of ergosterol in C. albicans or C. neoformans. It increased leakage of substances that absorb at 260 nm. Conclusions. The synthetic β-carboline 8-nitroharmane significantly inhibits pathogenic Cryptococcus species and is interesting as a lead compound towards new therapy for Cryptococcus infections. © 2019 Kátia Santana Cruz et al.Volume 2019Attribution-NonCommercial-NoDerivs 3.0 Brazilhttp://creativecommons.org/licenses/by-nc-nd/3.0/br/info:eu-repo/semantics/openAccessScreening and antifungal activity of a β-carboline derivative against cryptococcus neoformans and C. gattiiinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleInternational Journal of Microbiologyengreponame:Repositório Institucional do INPAinstname:Instituto Nacional de Pesquisas da Amazônia (INPA)instacron:INPAORIGINALartigo-inpa.pdfartigo-inpa.pdfapplication/pdf1381573https://repositorio.inpa.gov.br/bitstream/1/15581/1/artigo-inpa.pdf0d8a834463f89a5f09f460f0383c3bedMD511/155812020-05-14 20:46:12.809oai:repositorio:1/15581Repositório de PublicaçõesPUBhttps://repositorio.inpa.gov.br/oai/requestopendoar:2020-05-15T00:46:12Repositório Institucional do INPA - Instituto Nacional de Pesquisas da Amazônia (INPA)false |
dc.title.en.fl_str_mv |
Screening and antifungal activity of a β-carboline derivative against cryptococcus neoformans and C. gattii |
title |
Screening and antifungal activity of a β-carboline derivative against cryptococcus neoformans and C. gattii |
spellingShingle |
Screening and antifungal activity of a β-carboline derivative against cryptococcus neoformans and C. gattii Cruz, Kátia Santana |
title_short |
Screening and antifungal activity of a β-carboline derivative against cryptococcus neoformans and C. gattii |
title_full |
Screening and antifungal activity of a β-carboline derivative against cryptococcus neoformans and C. gattii |
title_fullStr |
Screening and antifungal activity of a β-carboline derivative against cryptococcus neoformans and C. gattii |
title_full_unstemmed |
Screening and antifungal activity of a β-carboline derivative against cryptococcus neoformans and C. gattii |
title_sort |
Screening and antifungal activity of a β-carboline derivative against cryptococcus neoformans and C. gattii |
author |
Cruz, Kátia Santana |
author_facet |
Cruz, Kátia Santana Lima, Emerson Silva Silva, Marcia de Jesus Amazonas da Souza, Érica Simplício de Montoia, Andréia Pohlit, Adrian Martin Souza, João Vicente Braga de |
author_role |
author |
author2 |
Lima, Emerson Silva Silva, Marcia de Jesus Amazonas da Souza, Érica Simplício de Montoia, Andréia Pohlit, Adrian Martin Souza, João Vicente Braga de |
author2_role |
author author author author author author |
dc.contributor.author.fl_str_mv |
Cruz, Kátia Santana Lima, Emerson Silva Silva, Marcia de Jesus Amazonas da Souza, Érica Simplício de Montoia, Andréia Pohlit, Adrian Martin Souza, João Vicente Braga de |
description |
Background. Cryptococcosis is a fungal disease of bad prognosis due to its pathogenicity and the toxicity of the drugs used for its treatment. The aim of this study was to investigate the medicinal potential of carbazole and β-carboline alkaloids and derivatives against Cryptococcus neoformans and C. gattii. Methods. MICs were established in accordance with the recommendations of the Clinical and Laboratory Standards Institute for alkaloids and derivatives against C. neoformans and C. gattii genotypes VNI and VGI, respectively. A single active compound was further evaluated against C. neoformans genotypes VNII, VNIII, and VNIV, C. gattii genotypes VGI, VGIII, and VGIV, Candida albicans ATCC 36232, for cytotoxicity against the MRC-5 lineage of human fibroblasts and for effects on fungal cells (cell wall, ergosterol, and leakage of nucleic acids). Results. Screening of 11 compounds revealed 8-nitroharmane as a significant inhibitor (MIC 40 μg/mL) of several C. neoformans and C. gattii genotypes. It was not toxic to fibroblasts (IC 50 > 50 μg/mL) nor did it alter fungal cell walls or the concentration of ergosterol in C. albicans or C. neoformans. It increased leakage of substances that absorb at 260 nm. Conclusions. The synthetic β-carboline 8-nitroharmane significantly inhibits pathogenic Cryptococcus species and is interesting as a lead compound towards new therapy for Cryptococcus infections. © 2019 Kátia Santana Cruz et al. |
publishDate |
2019 |
dc.date.issued.fl_str_mv |
2019 |
dc.date.accessioned.fl_str_mv |
2020-05-15T00:09:40Z |
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2020-05-15T00:09:40Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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https://repositorio.inpa.gov.br/handle/1/15581 |
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10.1155/2019/7157845 |
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https://repositorio.inpa.gov.br/handle/1/15581 |
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10.1155/2019/7157845 |
dc.language.iso.fl_str_mv |
eng |
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eng |
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Volume 2019 |
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Attribution-NonCommercial-NoDerivs 3.0 Brazil http://creativecommons.org/licenses/by-nc-nd/3.0/br/ info:eu-repo/semantics/openAccess |
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Attribution-NonCommercial-NoDerivs 3.0 Brazil http://creativecommons.org/licenses/by-nc-nd/3.0/br/ |
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openAccess |
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International Journal of Microbiology |
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International Journal of Microbiology |
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