Exposure of to Mebendazole Leads to Inhibition of Fungal Energy Production

Overview

Journal Antibiotics (Basel)

Specialty Pharmacology

Date 2023 Feb 25

PMID 36830117

Authors

Olivia Basso Rocha

Kleber Santiago Freitas E Silva

Dayane Moraes

Clayton Luiz Borges

Celia Maria de Almeida Soares

Maristela Pereira

Affiliations

Soon will be listed here.

Abstract

Paracoccidioidomycosis (PCM) is a fungal disease caused by organisms of the genus spp. The treatment of the disease is lengthy and includes several adverse effects. Various methodologies focus on the search for new treatments against fungal disease, including the repositioning of drugs. Our group showed the fungicidal effect of mebendazole in cells. Thus, understanding the effect of exposing fungal cells to mebendazole is significant for further studies in order to demonstrate it as a potential drug for the treatment of PCM. A proteomic analysis of exposed to mebendazole was carried out. Analyses showed that exposure strongly affected the pathways related to energy production, such as glycolysis, fermentation, and the electron transport chain. The quantification of adenosine triphosphate (ATP) and mitochondrial activity demonstrated that the drug alters the electron chain, resulting in an increase in oxidative stress. Enzymes such as superoxide dismutase (SOD) and cytochrome c oxidase (Cyt C) were repressed in cells exposed to mebendazole. The concentration of ethanol produced by the cells under treatment demonstrated that the attempt to produce energy through fermentation is also arrested. Thus, the drug inhibits fungal growth through changes in energy metabolism, making it a promising compound for use in the treatment of PCM.

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