Antifungal potential of usnic acid and alizarin against Paracoccidioides brasiliensis yeasts.

• Grant number: 25/13771-2
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2025
• End date: September 30, 2026
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Flávio Vieira Loures
• Grantee: Flávio Vieira Loures
• Host Institution: Instituto de Ciência e Tecnologia (ICT). Universidade Federal de São Paulo (UNIFESP). Campus São José dos Campos. São José dos Campos , SP, Brazil
• City of the host institution: São José dos Campos
• Associated research grant: 23/15407-0 - Association of antifungals with inhibitory mechanisms of immunosuppression in Paracoccidioidomycosis: depletion of Myeloid-derived Suppressor Cells (MDSCs) and inhibition of PD-1 and CTLA-4 checkpoint receptors., AP.R
• Associated scholarship(s): 25/23847-6 - Antifungal activity of usnic acid and alizarin against Paracoccidioides brasiliensis yeasts, BP.IC

Abstract

Paracoccidioidomycosis (PCM) is a systemic mycosis endemic in South America, especially in Brazil. Current treatment with antifungals such as amphotericin B and itraconazole has limitations, including long duration and significant adverse effects. Amphotericin B, in particular, is associated with renal, hepatic, and hematologic toxicities, which can compromise patient adherence and recovery. In this scenario, natural compounds such as alizarin and usnic acid have emerged as promising therapeutic alternatives, demonstrating antimicrobial activity against several fungi, including Candida spp., Cryptococcus spp., Aspergillus spp., Malassezia furfur, Microsporum gypseum, and Trichophyton mentagrophytes. Usnic acid, a dibenzofuran derivative found in lichens of the genus Usnea, and alizarin, an anthraquinone extracted from plants, also have antioxidant, antileukemic, and antiviral properties. This project aims to characterize the antifungal potential of these compounds against Paracoccidioides brasiliensis through in vitro assays to evaluate fungistatic and fungicidal activity, based on optical density, flow cytometry, and colony-forming units (CFU). If effective, they will be evaluated in a murine PCM model, with histological analysis and determination of CFU in target organs of mice treated or not with the compounds. Preliminary results indicate a significant reduction in colonies after 24 hours of treatment with both compounds, with performance comparable to that of amphotericin B, justifying the study. (AU)