Development of an antifungal prototype nanostructured lipid against Paracoccidioides brasiliensis and Paracoccidioides lutzii biofilms and assessment of toxicity in zebrafish animal model

• Grant number: 16/05581-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2016
• End date: December 31, 2016
• Field of knowledge: Health Sciences - Pharmacy - Toxicological Analysis
• Principal Investigator: Ana Marisa Fusco Almeida
• Grantee: Giovana Garcia Ferin
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Paracoccidioides spp is an important human pathogen that causes paracoccidioidomicose (PCM), a systemic mycosis with large distribution in Latin America, which makes it a public health issue. Recently, our group reported the ability of Paracoccidioides brasiliensis and P. Lutzii isolates to form in vitro biofilms, and a significant increase of the expression of genes involved in the virulence of the fungus in form of biofilm was verified. Based on the recent finds, in order to obtain better comprehension of the paracoccidioidomicose pathogenesis, as well as the use of new therapeutic approaches, the aim of this study is the development of new antifungal prototypes against P. Brasiliensis, P. Lutzii and their biofilms through the association of a T-chalcone molecule in a lipid nanostructured system, in addition to the study of the in vitro cytotoxicity from human cellular strains and in vivo toxicity in alternative Zebrafish animal model. Isolates of P. Brasiliensis and P. Lutzii phylogenetic species will be used in the development of trials for evaluation of antifungal activity of the compounds T-chalcone and T-chalcone incorporated in lipid nanostructured system against planktonic forms and biofilms, per microdilution technique, using as control of treatment amphotericin B and intraconazol. The antifungal activity will also be determined by trials for damage evaluation in biofilms per scanning electronic microscopy. The metabolic activity of biofilms will be evaluated by the trial of XTT reduction, both treated and untreated biofilms. Lastly, the in vivo toxicity of Zebrafish embryos will be evaluated, in order to observe morphological alterations (teratogenic analysis) and determine the concentration that leads to the death of 50% of the embryos (DL50). (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MEDINA-ALARCON, KAILA P.; SINGULANI, JUNYA DE L.; DUTRA, LUIZ A.; PITANGUI, NAYLA DE S.; PEREIRA-DA-SILVA, MARCELO A.; DOS SANTOS, MARIANA B.; AYUSSO, GABRIELA M.; REGASINI, LUIS O.; SOARES, CHRISTIANE P.; CHORILLI, MARLUS; et al. Antifungal activity of 2 '-hydroxychalcone loaded in nanoemulsion against Paracoccidioides spp.. FUTURE MICROBIOLOGY, v. 15, n. 1, p. 13-pg., 2020-01-01. (16/05581-0)

MEDINA-ALARCON, KAILA P.; SINGULANI, JUNYA DE L.; DUTRA, LUIZ A.; PITANGUI, NAYLA DE S.; PEREIRA-DA-SILVA, MARCELO A.; DOS SANTOS, MARIANA B.; AYUSSO, GABRIELA M.; REGASINI, LUIS O.; SOARES, CHRISTIANE P.; CHORILLI, MARLUS; et al. Antifungal activity of 2 `-hydroxychalcone loaded in nanoemulsion against Paracoccidioides spp.. FUTURE MICROBIOLOGY, v. 15, n. 1, p. 21-33, JAN 2020. (16/05581-0)