Drimane Sesquiterpene Aldehydes Control Candida Yeast Isolated from Candidemia in Chilean Patients

Drimys winteri J.R. (Winteraceae) produce drimane sesquiterpenoids with activity against Candida yeast. In this work, drimenol, polygodial (1), isotadeonal (2), and a new drimane α,β-unsaturated 1,4-dialdehyde, named winterdial (4), were purified from barks of D. winteri. The oxidation of drimenol produced the monoaldehyde drimenal (3). These four aldehyde sesquiterpenoids were evaluated against six Candida species isolated from candidemia patients in Chilean hospitals. Results showed that 1 displays fungistatic activity against all yeasts (3.75 to 15.0 µg/mL), but irritant effects on eyes and skin, whereas its non-pungent epimer 2 has fungistatic and fungicide activities at 1.9 and 15.0 µg/mL, respectively. On the other hand, compounds 3 and 4 were less active. Molecular dynamics simulations suggested that compounds 1–4 are capable of binding to the catalytic pocket of lanosterol 14-alpha demethylase with similar binding free energies, thus suggesting a potential mechanism of action through the inhibition of ergosterol synthesis. According to our findings, compound 2 appears as a valuable molecular scaffold to pursue the future development of more potent drugs against candidiasis with fewer side effects than polygodial. These outcomes are significant to broaden the alternatives to treat fungal infections with increasing prevalence worldwide using natural compounds as a primary source for active compounds. © 2022 by the authors.

Notas

Indexación: Scopus.

Palabras clave

Candida yeast, Drimane sesquiterpenoids, Drimys winteri, Isotadeonal, Lanosterol 14-α-demethylase, Molecular dynamics, Winterdial

Citación

International Journal of Molecular Sciences, Volume 23, Issue 19, October 2022, Article number 11753

DOI

10.3390/ijms231911753

URI

https://repositorio.unab.cl/xmlui/handle/ria/51746

Colecciones

FCE - Artículos de Revista

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