Dados do Trabalho

Título

REPURPOSING DRUG FOR INHIBITION OF ASPERGILLUS SPP.

Fundamentação/Introdução

Introduction: Drug repositioning or repurposing is a new methodology growing rapidly that allows new indications for previously approved drugs, failed, abandoned, advanced clinical candidates or whose targets that have already been discovered. Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) is an organoselenium compound that is known to possess anti-atherosclerotic, anti-inflammatory, antioxidative, cytoprotective, anti-mutagenic and anti-lipid peroxidative properties. However, the antifungal activity of Ebselen (EBS) against Aspergillus fumigatus has not been characterized thus far. The specie main causative of invasive aspergillosis (IA) is A. fumigatus followed by A. flavus, A. niger, A. terreus and A. nidulans. The antifungal drugs available for IA treatment are not very effective in vivo as the mortality rate of patients who receive antifungal therapy is up to 50%. Thus, the search for alternative therapies and/or developing more specific antifungal agents has become increasingly imperative.

Objetivos

Objective: To evaluate the antifungal activity of EBS against Aspergillus spp.

Delineamento e Métodos

Methods: Reference strain and one isolate of A. fumigatus and one isolate of A. flavus were used. Broth microdilution assay was performed to determine the minimum inhibitory concentration (MIC) of EBS (0.5-256.0 µg/mL) and commercial antifungal agents: voriconazole (VOR) and amphotericin B (AMB) (0.03-16.0 µg/mL) following the Clinical & Laboratory Standards Institute (CLSI) M38-A2 protocol. Resazurin were used to determine MIC (100% growth reduction) after 48h incubation at 35°C.

Resultados

Results: Both A. fumigatus strains showed MIC for EBS (4.0 µg/mL), VOR (0.25 µg/mL) and AMB (0.25 µg/mL). A. flavus isolate showed less sensitivity for the antifungals tested, presenting MIC for EBS (8.0 µg/mL), VOR (0.5 µg/mL) and AMB (1.0 µg/mL).

Conclusões/Considerações Finais

Conclusion: EBS showed to be a promising repurposing drug for the treatment of IA with MIC in vitro encouraging further investigations with in vivo models for inhibition of Aspergillus spp.

Palavras-chave

Aspergillus spp., ebselen, drug repositioning