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Evaluation of new therapies and biomarkers in paracoccidioidomycosis: antifungal activity of alkyl gallates in alternative models and mice and identification of circulating microRNAs

Grant number: 14/10446-9
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): September 01, 2014
Effective date (End): February 28, 2017
Field of knowledge:Health Sciences - Pharmacy
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Maria José Soares Mendes Giannini
Grantee:Junya de Lacorte Singulani
Home Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

The search for new therapies and new biomarkers are needed in fungal diseases such as paracoccidioidomycosis (PCM). The PCM is a systemic mycosis caused by fungi of the genus Paracoccidioides and appears endemic in Central and South America. Despite the good efficacy of antifungal agents against P. brasiliensis and P. lutzii, some of them such as amphotericin B can be toxic to the host cells. Furthermore, it was described the occurrence of P. brasiliensis isolates resistant to ketoconazole. In this context, the search for natural products with improved antifungal efficacy and safety have increased. Additionally, alternative models as Galleria mellonella and Caenorhabditis elegans have been used to study the fungus-host interaction and for search of new therapies in a simple way and on large scale. In this work, G. mellonella and C. elegans will be infected by different concentrations of Paracoccidioides spp. and efficacy of drugs amphotericin B, itraconazole and esters of gallic acid derivatives will be evaluated. For such purpose the survival and fungal burden in these models will be evaluated and subsequently the compound with best activity in alternative models will be evaluated for efficacy, toxicology and pharmacokinetics in mice. Another important aspect of this work relates to the search for new biomarkers such as circulating microRNAs. MicroRNAs are small non-coding RNAs that play critical roles in most biological processes and also in the pathophysiology of diseases. Thus, it will be performed the identification of RNAs in serum of patients and mice with PCM and subsequent screening of microRNAs by quantitative PCR. The search for genes and pathways related to microRNAs will be identified by bioinformatics. Statistical analysis of all results will be made at Graph Pad Prism 5. (AU)

Scientific publications (10)
(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)
SCORZONI, LILIANA; ALVES DE PAULA E SILVA, ANA CAROLINA; DE OLIVEIRA, HAROLDO CESAR; DOS SANTOS, CLAUDIA TAVARES; SINGULANI, JUNYA DE LACORTE; ASSATO, PATRICIA AKEMI; MARCOS, CAROLINE MARIA; OLIVEIRA, LARIANE TEODORO; FREGONEZI, NATHALIA FERREIRA; PEREIRA ROSSI, DIEGO CONRADO; ROQUE DA SILVA, LEANDRO BUFFONI; TABORDA, CARLOS PELLESCHI; FUSCO-ALMEIDA, ANA MARISA; SOARES MENDES-GIANNINI, MARIA JOSE. In Vitro and In Vivo Effect of Peptides Derived from 14-3-3 Paracoccidioides spp. Protein. JOURNAL OF FUNGI, v. 7, n. 1 JAN 2021. Web of Science Citations: 0.
MARCOS, CAROLINE MARIA; TAMER, GABRIELLE; DE OLIVEIRA, HAROLDO CESAR; ASSATO, PATRICIA AKEMI; SCORZONI, LILIANA; SANTOS, CLAUDIA TAVARES; SINGULANI, JUNYA DE LACORTE; DA SILVA, JULHIANY DE FATIMA; DE ALMEIDA, RODRIGO; ALVES DE PAULA E SILVA, ANA CAROLINA; MORAES DA SILVA, ROSANGELA APARECIDA; DE ANDRADE, CLEVERTON ROBERTO; TAMAYO, DIANA PATRICIA; LOPEZ, ANGELA MARIA; BARBOSA, NATALIA MOREIRA; ZANELLI, CLESLEI FERNANDO; HERNANDEZ-RUIZ, ORVILLE; MCEWEN, JUAN G.; SOARES MENDES-GIANNINI, MARIA JOSE; FUSCO-ALMEIDA, ANA MARISA. Down-regulation of TUFM impairs host cell interaction and virulence by Paracoccidioides brasiliensis. SCIENTIFIC REPORTS, v. 9, NOV 20 2019. Web of Science Citations: 0.
SINGULANI, JUNYA DE LACORTE; SCORZONI, LILIANA; STROHMAYER LOURENCETTI, NATALIA MANUELA; OLIVEIRA, LUANA ROSSI; CONCOARO, ROSANA SILVA; DA SILVA, PATRICIA BENTO; NAZARE, ANA CAROLINA; POLAQUINI, CARLOS ROBERTO; VICTORELLI, FRANCESCA DAMIANI; CHORILLI, MARLUS; REGASINI, LUIS OCTAVIO; FUSCO ALMEIDA, ANA MARISA; SOARES MENDES GIANNINI, MARIA JOSE. Potential of the association of dodecyl gallate with nanostructured lipid system as a treatment for paracoccidioidomycosis: In vitro and in vivo efficacy and toxicity. International Journal of Pharmaceutics, v. 547, n. 1-2, p. 630-636, AUG 25 2018. Web of Science Citations: 1.
SCORZONI, LILIANA; ALVES DE PAULA E SILVA, ANA CAROLINA; DE OLIVEIRA, HAROLDO CESAR; MARCOS, CAROLINE MARIA; SINGULANI, JUNYA DE LACORTE; FUSCO-ALMEIDA, ANA MARISA; SOARES MENDES-GIANNINI, MARIA JOSE. Can passage in Galleria mellonella activate virulence factors of Paracoccidioides brasiliensis as in the murine model?. Medical Mycology, v. 56, n. 3, p. 374-377, APR 2018. Web of Science Citations: 2.
SCORZONI, LILIANA; PILAR DE LUCAS, MARIA; SINGULANI, JUNYA DE LACORTE; DE OLIVEIRA, HAROLDO CESAR; ASSATO, PATRICIA AKEMI; FUSCO-ALMEIDA, ANA MARISA; SOARES MENDES-GIANNINI, MARIA JOSE. Evaluation of &ITCaenorhabditis elegans&IT as a host model for &ITParacoccidioides brasiliensis &ITand &ITParacoccidioides lutzii&IT. PATHOGENS AND DISEASE, v. 76, n. 1 FEB 2018. Web of Science Citations: 1.
PALANCO, ANA CERREJN; SINGULANI, JUNYA DE LACORTE; COSTA-ORLANDI, CAROLINE BARCELOS; GULLO, FERNANDA PATRICIA; STROHMAYER LOURENCETTI, NATALIA MANUELA; GOMES, PAULO CESAR; AYUSSO, GABRIELA MIRANDA; DUTRA, LUIZ ANTONIO; BOLZANI, VANDERLAN DA SILVA; REGASINI, LUIS OCTAVIO; SOARES MENDES-GIANNINI, MARIA JOSE; FUSCO-ALMEIDA, ANA MARISA. Activity of 3 `-hydroxychalcone against Cryptococcus gattii and toxicity, and efficacy in alternative animal models. FUTURE MICROBIOLOGY, v. 12, n. 13, p. 1123-1134, OCT 2017. Web of Science Citations: 9.
SINGULANI, JUNYA DE LACORTE; SCORZONI, LILIANA; GOMES, PAULO CESAR; NAZARE, ANA CAROLINA; POLAQUINI, CARLOS ROBERTO; REGASINI, LUIS OCTAVIO; FUSCO-ALMEIDA, ANA MARISA; SOARES MENDES-GIANNINI, MARIA JOSE. Activity of gallic acid and its ester derivatives in Caenorhabditis elegans and zebrafish (Danio rerio) models. Future Medicinal Chemistry, v. 9, n. 16, p. 1863-1872, OCT 2017. Web of Science Citations: 6.
SINGULANI, JUNYA DE LACORTE; DA SILVA, JULHIANY DE FATIMA; GULLO, FERNANDA PATRICIA; COSTA, MARINA CELIA; FUSCO-ALMEIDA, ANA MARISA; ENGUITA, FRANCISCO JAVIER; SOARES MENDES-GIANNINI, MARIA JOSE. Preliminary evaluation of circulating microRNAs as potential biomarkers in paracoccidioidomycosis. BIOMEDICAL REPORTS, v. 6, n. 3, p. 353-357, MAR 2017. Web of Science Citations: 3.
SANGALLI-LEITE, FERNANDA; SCORZONI, LILIANA; ALVES DE PAULA E SILVA, ANA CAROLINA; DA SILVA, JULHIANY DE FATIMA; DE OLIVEIRA, HAROLDO CESAR; SINGULANI, JUNYA DE LACORTE; GULLO, FERNANDA PATRICIA; DA SILVA, ROSANGELA MORAES; REGASINI, LUIS OCTAVIO; SIQUEIRA DA SILVA, DULCE HELENA; BOLZANI, VANDERLAN DA SILVA; FUSCO-ALMEIDA, ANA MARISA; SOARES MENDES-GIANNINI, MARIA JOSE. Synergistic effect of pedalitin and amphotericin B against Cryptococcus neoformans by in vitro and in vivo evaluation. INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, v. 48, n. 5, p. 504-511, NOV 2016. Web of Science Citations: 9.
SINGULANI, JUNYA DE LACORTE; SCORZONI, LILIANA; ALVES DE PAULA E SILVA, ANA CAROLINA; FUSCO-ALMEIDA, ANA MARISA; SOARES MENDES-GIANNINI, MARIA JOSE. Evaluation of the efficacy of antifungal drugs against Paracoccidioides brasiliensis and Paracoccidioides lutzii in a Galleria mellonella model. INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, v. 48, n. 3, p. 292-297, SEP 2016. Web of Science Citations: 11.

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