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

• Published in: Journal of Venomous Animals and Toxins including Tropical Diseases
• Main Authors: Adriele Dandara Levorato Vinche, Iván de- la-Cruz-Chacón, Alma Rosa González-Esquinca, Julhiany de Fátima da Silva, Gisela Ferreira, Daniela Carvalho dos Santos, Hans Garcia Garces, Daniela Vanessa Moris de Oliveira, Camila Marçon, Ricardo de Souza Cavalcante, Rinaldo Poncio Mendes
• Format: Article in Journal/Newspaper
• Language: English
• Published: SciELO 2020
• Subjects: Liriodenine; Paracoccidioidomycosis; Systemic mycosis; Antifungal compounds; Antimicrobial compounds; Medicinal plants; Arctic medicine. Tropical medicine; RC955-962; Toxicology. Poisons; RA1190-1270; Zoology; QL1-991; Arctic
• Online Access: https://doi.org/10.1590/1678-9199-jvatitd-2020-0023; https://doaj.org/article/d6fa12a6fbcf455085eb0a330add4b04

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 non-infectious 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.