Título:	Antifungal activity of sustainable histone deacetylase inhibitors against planktonic cells and biofilms of Candida spp. and Cryptococcus neoformans
Autor(es):	Oliveira, Andressa Souza de Oliveira, Jonathas Sales de Kumar, Rajender Silva, Fabiana Brandão Alves Fernandes, Mirele Rodrigues Nobre, Feynman Dias Costa, Anderson da Cunha Albuquerque, Patrícia Sidrim, José Júlio Costa Rocha, Marcos Fábio Gadelha Santos, Flavia Almeida Srivastava, Vaibhav Romeiro, Luiz Antonio Soares Brilhante, Raimunda Sâmia Nogueira
Afiliação do autor:	University of Brasilia, Faculty of Medicine, Tropical Medicine Centre, Laboratory of Development of Therapeutic Innovations University of Brasilia, Faculty of Health Sciences, Postgraduate Program in Pharmaceutical Sciences Federal University of Ceará, Department of Pathology and Legal Medicine, Postgraduate Program in Medical Microbiology, Specialized Medical Mycology Centre AlbaNova University Center, KTH Royal Institute of Technology, School of Engineering Sciences in Chemistry, Biotechnology and Health, Department of Chemistry, Division of Glycoscience University of Brasilia, Faculty of Medicine, Postgraduate Program in Tropical Medicine Federal University of Ceará, Department of Pathology and Legal Medicine, Postgraduate Program in Medical Microbiology, Specialized Medical Mycology Centre Federal University of Ceará, Department of Pathology and Legal Medicine, Postgraduate Program in Medical Microbiology, Specialized Medical Mycology Centre Federal University of Ceará, Department of Pathology and Legal Medicine, Postgraduate Program in Medical Microbiology, Specialized Medical Mycology Centre University of Brasília. Campus Ceilândia Federal University of Ceará, Department of Pathology and Legal Medicine, Postgraduate Program in Medical Microbiology, Specialized Medical Mycology Centre Federal University of Ceará, Department of Pathology and Legal Medicine, Postgraduate Program in Medical Microbiology, Specialized Medical Mycology Centre Federal University of Ceará, Department of Physiology and Pharmacology, Laboratory of Natural Products AlbaNova University Center, KTH Royal Institute of Technology, School of Engineering Sciences in Chemistry, Biotechnology and Health, Department of Chemistry, Division of Glycoscience University of Brasilia, Faculty of Medicine, Tropical Medicine Centre, Laboratory of Development of Therapeutic Innovations University of Brasilia, Faculty of Health Sciences, Postgraduate Program in Pharmaceutical Sciences University of Brasilia, Faculty of Medicine, Postgraduate Program in Tropical Medicine Federal University of Ceará, Department of Pathology and Legal Medicine, Postgraduate Program in Medical Microbiology, Specialized Medical Mycology Centre
Assunto:	Antifúngicos Inibidores de histonas desacetilases Ácido hidroxâmico Biofilme
Data de publicação:	8-Ago-2023
Editora:	Oxford University Press on behalf of The International Society for Human and Animal Mycology
Referência:	OLIVEIRA, Andressa Souza de et al. Antifungal activity of sustainable histone deacetylase inhibitors against planktonic cells and biofilms of Candida spp. and Cryptococcus neoformans. Medical Mycology, [S. l.], v. 61, n. 8, myad073, ago. 2023. DOI: https://doi.org/10.1093/mmy/myad073.
Abstract:	The 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.
Unidade Acadêmica:	Faculdade de Medicina (FM) Faculdade de Ciências da Saúde (FS) Departamento de Farmácia (FS FAR)
Programa de pós-graduação:	Programa de Pós-Graduação em Ciências Farmacêuticas Programa de Pós-Graduação em Medicina Tropical
DOI:	https://doi.org/10.1093/mmy/myad073
Versão da editora:	https://academic.oup.com/mmy/article/61/8/myad073/7239295
Aparece nas coleções:	Artigos publicados em periódicos e afins

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