Antifungal activity of sustainable histone deacetylase inhibitors against planktonic cells and biofilms of Candida spp. and Cryptococcus neoformans

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Autor(es): dc.contributorUniversity of Brasilia, Faculty of Medicine, Tropical Medicine Centre, Laboratory of Development of Therapeutic Innovations-
Autor(es): dc.contributorUniversity of Brasilia, Faculty of Health Sciences, Postgraduate Program in Pharmaceutical Sciences-
Autor(es): dc.contributorFederal University of Ceará, Department of Pathology and Legal Medicine, Postgraduate Program in Medical Microbiology, Specialized Medical Mycology Centre-
Autor(es): dc.contributorAlbaNova University Center, KTH Royal Institute of Technology, School of Engineering Sciences in Chemistry, Biotechnology and Health, Department of Chemistry, Division of Glycoscience-
Autor(es): dc.contributorUniversity of Brasilia, Faculty of Medicine, Postgraduate Program in Tropical Medicine-
Autor(es): dc.contributorFederal University of Ceará, Department of Pathology and Legal Medicine, Postgraduate Program in Medical Microbiology, Specialized Medical Mycology Centre-
Autor(es): dc.contributorFederal University of Ceará, Department of Pathology and Legal Medicine, Postgraduate Program in Medical Microbiology, Specialized Medical Mycology Centre-
Autor(es): dc.contributorFederal University of Ceará, Department of Pathology and Legal Medicine, Postgraduate Program in Medical Microbiology, Specialized Medical Mycology Centre-
Autor(es): dc.contributorUniversity of Brasília. Campus Ceilândia-
Autor(es): dc.contributorFederal University of Ceará, Department of Pathology and Legal Medicine, Postgraduate Program in Medical Microbiology, Specialized Medical Mycology Centre-
Autor(es): dc.contributorFederal University of Ceará, Department of Pathology and Legal Medicine, Postgraduate Program in Medical Microbiology, Specialized Medical Mycology Centre-
Autor(es): dc.contributorFederal University of Ceará, Department of Physiology and Pharmacology, Laboratory of Natural Products-
Autor(es): dc.contributorAlbaNova University Center, KTH Royal Institute of Technology, School of Engineering Sciences in Chemistry, Biotechnology and Health, Department of Chemistry, Division of Glycoscience-
Autor(es): dc.contributorUniversity of Brasilia, Faculty of Medicine, Tropical Medicine Centre, Laboratory of Development of Therapeutic Innovations-
Autor(es): dc.contributorUniversity of Brasilia, Faculty of Health Sciences, Postgraduate Program in Pharmaceutical Sciences-
Autor(es): dc.contributorUniversity of Brasilia, Faculty of Medicine, Postgraduate Program in Tropical Medicine-
Autor(es): dc.contributorFederal University of Ceará, Department of Pathology and Legal Medicine, Postgraduate Program in Medical Microbiology, Specialized Medical Mycology Centre-
Autor(es): dc.creatorOliveira, Andressa Souza de-
Autor(es): dc.creatorOliveira, Jonathas Sales de-
Autor(es): dc.creatorKumar, Rajender-
Autor(es): dc.creatorSilva, Fabiana Brandão Alves-
Autor(es): dc.creatorFernandes, Mirele Rodrigues-
Autor(es): dc.creatorNobre, Feynman Dias-
Autor(es): dc.creatorCosta, Anderson da Cunha-
Autor(es): dc.creatorAlbuquerque, Patrícia-
Autor(es): dc.creatorSidrim, José Júlio Costa-
Autor(es): dc.creatorRocha, Marcos Fábio Gadelha-
Autor(es): dc.creatorSantos, Flavia Almeida-
Autor(es): dc.creatorSrivastava, Vaibhav-
Autor(es): dc.creatorRomeiro, Luiz Antonio Soares-
Autor(es): dc.creatorBrilhante, Raimunda Sâmia Nogueira-
Data de aceite: dc.date.accessioned2024-07-22T11:50:19Z-
Data de disponibilização: dc.date.available2024-07-22T11:50:19Z-
Data de envio: dc.date.issued2024-05-28-
Data de envio: dc.date.issued2024-05-28-
Data de envio: dc.date.issued2023-08-08-
Fonte completa do material: dc.identifierhttp://repositorio2.unb.br/jspui/handle/10482/48134-
Fonte completa do material: dc.identifierhttps://doi.org/10.1093/mmy/myad073-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/capes/790001-
Descrição: dc.descriptionThe limited therapeutic options for fungal infections and the increased incidence of fungal strains resistant to antifungal drugs, especially Candida spp., require the development of new antifungal drugs and strategies. Histone deacetylase inhibitors (HDACi), like vorinostat, have been studied in cancer treatment and have antifungal effects, acting alone or synergistically with classical antifungals. Here we investigated the antifungal activity of two novel sustainable HDACi (LDT compounds) based on vorinostat structure. Molecular docking simulation studies reveal that LDT compounds can bind to Class-I HDACs of Candida albicans, C. tropicalis, and Cryptococcus neoformans, which showed similar binding mode to vorinostat. LDT compounds showed moderate activity when tested alone against fungi but act synergistically with antifungal azoles against Candida spp. They reduced biofilm formation by more than 50% in C. albicans (4 μg/mL), with the main action in fungal filamentation. Cytotoxicity of the LDT compounds against RAW264.7 cells was evaluated and LDT536 demonstrated cytotoxicity only at the concentration of 200 μmol/L, while LDT537 showed IC50 values of 29.12 μmol/L. Our data indicated that these sustainable and inexpensive HDACi have potential antifungal and antibiofilm activities, with better results than vorinostat, although further studies are necessary to better understand the mechanism against fungal cells.-
Descrição: dc.descriptionFaculdade de Medicina (FM)-
Descrição: dc.descriptionFaculdade de Ciências da Saúde (FS)-
Descrição: dc.descriptionDepartamento de Farmácia (FS FAR)-
Descrição: dc.descriptionPrograma de Pós-Graduação em Ciências Farmacêuticas-
Descrição: dc.descriptionPrograma de Pós-Graduação em Medicina Tropical-
Idioma: dc.languageen-
Publicador: dc.publisherOxford University Press on behalf of The International Society for Human and Animal Mycology-
Relação: dc.relationhttps://academic.oup.com/mmy/article/61/8/myad073/7239295-
Direitos: dc.rightsAcesso Restrito-
Palavras-chave: dc.subjectAntifúngicos-
Palavras-chave: dc.subjectInibidores de histonas desacetilases-
Palavras-chave: dc.subjectÁcido hidroxâmico-
Palavras-chave: dc.subjectBiofilme-
Título: dc.titleAntifungal activity of sustainable histone deacetylase inhibitors against planktonic cells and biofilms of Candida spp. and Cryptococcus neoformans-
Aparece nas coleções:Repositório Institucional – UNB

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