Antifungal activity of liriodenine on agents of systemic mycoses, with emphasis on the genus Paracoccidioides

 

Adriele Dandara Levorato Vinche1, Iván de-la-Cruz-Chacón2, Alma Rosa González-Esquinca2, Julhiany de Fátima da Silva1, Gisela Ferreira3, Daniela Carvalho dos Santos3, Hans Garcia Garces3, Daniela Vanessa Moris de Oliveira4, Camila Marçon1, Ricardo de Souza Cavalcante1, Rinaldo Poncio Mendes1

 

1 Department of Tropical Disease and Imaging Diagnosis, Botucatu Medical School, São Paulo State University (UNESP), Botucatu, SP, Brazil.

2 Universidad de Ciencias y Artes de Chiapas, Tuxtla Gutierrez, Chiapas, Mexico.

3 Institute of Biosciences of Botucatu, São Paulo State University (UNESP), Botucatu, SP, Brazil.

4 Faculdade de Ciências da Saúde, Universidade do Oeste Paulista (Unoeste), Presidente Prudente, SP, Brazil.

 

Abstract

Background: Endemic systemic mycoses remain a health challenge, since these opportunistic diseases are increasingly infecting immunosuppressed patients. The simultaneous use of antifungal compounds and other drugs to treat infectious or noninfectious diseases has led to several interactions and undesirable effects. Thus, new antifungal compounds should be investigated. The present study aimed to evaluate the activity of liriodenine extracted from Annona macroprophyllata on agents of systemic mycoses, with emphasis on the genus Paracoccidioides.

 

Methods: The minimum inhibitory concentration (MIC) and minimum fungicide concentration (MFC) were determined by the microdilution method. The cellular alterations caused by liriodenine on a standard P. brasiliensis (Pb18) strain were evaluated by transmission and scanning electron microscopy.

 

Results: Liriodenine was effective only in 3 of the 8 strains of the genus Paracoccidioides and in the Histoplasma capsulatum strain, in a very low concentration (MIC of 1.95 μg.mL-1); on yeasts of Candida spp. (MIC of 125 to 250 μg.mL-1), including C. krusei (250 μg.mL-1), which has intrinsic resistance to fluconazole; and in Cryptococcus neoformans and Cryptococcus gattii (MIC of 62.5 μg.mL-1). However, liriodenine was not effective against Aspergillus fumigatus at the studied concentrations. Liriodenine exhibited fungicidal activity against all standard strains and clinical isolates that showed to be susceptible by in vitro tests. Electron microscopy revealed cytoplasmic alterations and damage to the cell wall of P. brasiliensis (Pb18).

 

Conclusion: Our results indicate that liriodenine is a promising fungicidal compound that should undergo further investigation with some chemical modifications.

 

Keywords: Liriodenine Paracoccidioidomycosis Systemic mycosis Antifungal compounds Antimicrobial compounds Medicinal plants

 

Correspondence: adrielelevorato@yahoo.com.br

 

Received: 01 March 2020; Accepted: 06 October 2020; Published online: 28 October 2020