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.