Ent-hardwickiic acid from C. pubiflora and its microbial metabolites are more potent than fluconazole in vitro against Candida glabrata

Autor: M.V. Sousa Teixeira, L.M. Fernandes, V. Stefanelli de Paula, A.G. Ferreira, N.A. Jacometti Cardoso Furtado
Rok vydání: 2022
Předmět:
Zdroj: Letters in Applied Microbiology. 74:622-629
ISSN: 1472-765X
0266-8254
Popis: The incidence of Candida glabrata infections has rapidly grown and this species is among those responsible for causing invasive candidiasis with a high mortality rate. The diterpene ent-hardwickiic acid is a major constituent in Copaifera pubiflora oleoresin and the ethnopharmacological uses of this oleoresin by people from Brazilian Amazonian region point to a potential use of this major constituent as an antimicrobial. Therefore, the goal of this study was to evaluate the antifungal activity of ent-hardwickiic acid against Candida species and to produce derivatives of this diterpene by using microbial models for simulating the mammalian metabolism. The microbial transformations of ent-hardwickiic acid were carried out by Aspergillus brasiliensis and Cunninghamella elegans and hydroxylated metabolites were isolated and their chemical structures were determined. The antifungal activity of ent-hardwickiic acid and its metabolites was assessed by using the microdilution broth method in 96-well microplates and compared with that of fluconazole. All the diterpenes showed fungistatic effects (ranging from 19·7 to 75·2 µmol l−1) against C. glabrata at lower concentrations than fluconazole (163·2 µmol l−1) and were more potent fungicides (ranging from 39·5 to 150·4 µmol l−1) than fluconazole, which showed fungicidal effect at the concentration of 326·5 µmol l−1.
Databáze: OpenAIRE
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