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

Víctor Marín, Bryan Bart, Nicole Cortez, Verónica A. Jiménez, Víctor Silva, Oscar Leyton, Jaime R. Cabrera-Pardo, Bernd Schmidt, Matthias Heydenreich, Viviana Burgos, Cristian Paz

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

Resumen

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.

Idioma originalInglés
Número de artículo11753
PublicaciónInternational Journal of Molecular Sciences
Volumen23
N.º19
DOI
EstadoPublicada - oct. 2022

Áreas temáticas de ASJC Scopus

  • Catálisis
  • Biología molecular
  • Espectroscopia
  • Informática aplicada
  • Química física y teórica
  • Química orgánica
  • Química inorgánica

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