title: Inhibition of Paracoccidioides lutzii Pb01 isocitrate lyase by the natural compound argentilactone and its semi-synthetic derivatives.
abstract: The dimorphic fungus Paracoccidioides spp. is responsible for paracoccidioidomycosis, the most prevalent systemic mycosis in Latin America, causing serious public health problems. Adequate treatment of mycotic infections is difficult, since fungi are eukaryotic organisms with a structure and metabolism similar to those of eukaryotic hosts. In this way, specific fungus targets have become important to search of new antifungal compound. The role of the glyoxylate cycle and its enzymes in microbial virulence has been reported in many fungal pathogens, including Paracoccidioides spp. Here, we show the action of argentilactone and its semi-synthetic derivative reduced argentilactone on recombinant and native isocitrate lyase from Paracoccidioides lutzii Pb01 (PbICL) in the presence of different carbon sources, acetate and glucose. Additionally, argentilactone and its semi-synthetic derivative reduced argentilactone exhibited relevant inhibitory activity against P. lutzii Pb01 yeast cells and dose-dependently influenced the transition from the mycelium to yeast phase. The other oxygenated derivatives tested, epoxy argentilactone and diol argentilactone-, did not show inhibitory action on the fungus. The results were supported by in silico experiments.
authors.affiliation: Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
authors.forename: Renata Silva do
authors.initials: RS
authors.lastname: Prado
authors.affiliation: Laboratório de Produtos Naturais, Instituto de Química, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
authors.forename: Ricardo Justino
authors.initials: RJ
authors.lastname: Alves
authors.affiliation: Laboratório de Produtos Naturais, Instituto de Química, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
authors.forename: Cecília Maria Alves de
authors.initials: CM
authors.lastname: Oliveira
authors.affiliation: Laboratório de Produtos Naturais, Instituto de Química, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
authors.forename: Lucília
authors.initials: L
authors.lastname: Kato
authors.affiliation: Núcleo Colaborativo de BioSistemas, Campus Jataí, Universidade Federal de Goiás, Jataí, Goiás, Brazil.
authors.forename: Roosevelt Alves da
authors.initials: RA
authors.lastname: Silva
authors.affiliation: Núcleo Colaborativo de BioSistemas, Campus Jataí, Universidade Federal de Goiás, Jataí, Goiás, Brazil.
authors.forename: Guilherme Oliveira
authors.initials: GO
authors.lastname: Quintino
authors.affiliation: Instituto de Química, Departamento de Química Orgânica, Universidade Federal da Bahia, Salvador, Bahia, Brazil.
authors.forename: Silvio
authors.initials: S
authors.lastname: do Desterro Cunha
authors.affiliation: Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
authors.forename: Célia Maria
authors.initials: CM
authors.lastname: de Almeida Soares
authors.affiliation: Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
authors.forename: Maristela
authors.initials: M
authors.lastname: Pereira
mesh_terms: D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D007522:Isocitrate Lyase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D025282:Mycelium / Q000166:cytology / Q000187:drug effects; D010228:Paracoccidioides / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development; D012997:Solvents / Q000737:chemistry; D040681:Structural Homology, Protein; D013816:Thermodynamics
chemical_list: D004791:Enzyme Inhibitors; D007783:Lactones; D012997:Solvents; C108954:argentilactone; D007522:Isocitrate Lyase
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