Investigation of the antifungal activity and mechanism of action of 2-aryloxazolines derivatives on Candida albicans

• Grant number: 18/11612-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: April 01, 2019
• End date: January 31, 2023
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Kelly Ishida
• Grantee: Vinicius de Morais Barroso
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Systemic infections caused by fungi that a serious health risk and these have been increasing in recent decades, they are raising mortality and morbidity of the patients. Among these yeast, the Candida albicans accounts for 50%-70% of infections. Studies demonstrate, the appearance of resistant strains to the main antifungal agents in the treatment of candidiasis. New antifungal molecules are currently being researched, attending to new targets of action; the enzyme dihydrofolate reductase (DHFR) has being an interesting candidate. Inhibition of this enzyme leads to an interruption in folate biosynthesis, leading to deficiency in the tetrahydrofolate (THF) cofactor and it can induce the cell death. Antifolates are analogous compounds that interact with the DHFR enzyme site, which they modify and disrupt the folate pathway. Recently, our research group observed the antifungal effect of synthetic 2-aryloxazoline molecules (26 molecules) on the growth of Candida spp and inclusing the strains that are resistant to fluconazole. In addition, we hypothesized a possible interaction with the enzyme DHFR according to the molecular docking analysis. Thus, the present study aims to evaluate the antifungal efficiency and mechanism of action of 2-aryloxazolines derivatives on C. albicans. (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)

ARGOMEDO, LUIS M. Z.; BARROSO, VINICIUS M.; BARREIRO, CRISTIANE S.; DARBEM, MARIANA P.; ISHIDA, KELLY; STEFANI, HELIO A.. Novel 2-Aryloxazoline Compounds Exhibit an Inhibitory Effect on Candida spp., Including Antifungal-Resistant Isolates. ACS Medicinal Chemistry Letters, v. 11, n. 12, p. 2470-2475, DEC 10 2020. (18/11612-0, 17/19374-9)

KIRKMAN, TIM; SKETCHER, ALICE; BARROSO, VINICIUS DE MORAIS; ISHIDA, KELLY; TOSIN, MANUELA; BERTACINE DIAS, MARCIO VINICIUS. Crystal structure of dihydrofolate reductase from the emerging pathogenic fungus Candida auris. ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, v. 79, p. 11-pg., 2023-08-01. (21/01279-5, 20/03850-9, 18/11612-0)

CUNHA, MARIELTON DOS PASSOS; VILELA, ANA PAULA PESSOA; MOLINA, CAMILA VIEIRA; ACUNA, STEPHANIE MAIA; MUXEL, SANDRA MARCIA; BARROSO, VINICIUS DE MORAIS; BARONI, SABRINA; GOMES DE OLIVEIRA, LILIAN; ANGELO, YAN DE SOUZA; PERON, JEAN PIERRE SCHATZMANN; et al. Atypical Prolonged Viral Shedding With Intra-Host SARS-CoV-2 Evolution in a Mildly Affected Symptomatic Patient. FRONTIERS IN MEDICINE, v. 8, NOV 26 2021. (19/20708-4, 18/11612-0, 17/27131-9, 19/24518-5, 17/23519-2, 20/01487-4)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

BARROSO, Vinicius de Morais. Antifungal activity of 2-aryloxazoline derivatives and miltefosine on Candida spp. and inhibition of Candida albicans virulence factors. 2023. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.