Aim: Novel 4-methoxy-naphthalene derivatives were synthesized based on hits structures in order to evaluate the antifungal activity against Paracoccidioides spp. Methods: Antifungal activity of compounds was evaluated against P. brasiliensis and most promising compounds 2 and 3 were tested against eight clinically important fungal species. Results: Compound 3 was the more active compound with MIC 8 to 32 μg.ml-1 for Paracoccidioides spp without toxicity monkey kidney and murine macrophagecells. Carbohydrazide 3 showed good synergistic antifungal activity with amphotericin B against P. brasiliensis specie. Titration assay of carbohydrazide 3 with PbHSD enzyme demonstrates the binding ligand-protein. Molecular dynamics simulations show that ligand 3 let the PbHSD protein more stable. Conclusion: New carbohydrazide 3 is an attractive lead for drug development to treat paracoccidioidomycoses.
CITATION STYLE
Bagatin, M. C., Rozada, A. M. F., Rodrigues, F. A. V., Bueno, P. S. A., Santos, J. L., Canduri, F., … Gauze, G. F. (2019). New 4-methoxy-naphthalene derivatives as promisor antifungal agents for paracoccidioidomycosis treatment. Future Microbiology, 14(3), 235–245. https://doi.org/10.2217/fmb-2018-0276
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