Drimane Sesquiterpene Aldehydes Control Candida Yeast Isolated from Candidemia in Chilean Patients
| Primer Autor |
Paz, Cristian
|
| Co-autores |
Marin, Victor
Bart, Bryan
Cortez, Nicole
Jimenez, Veronica A.
Silva, Victor
Leyton, Oscar
Cabrera-Pardo, Jaime R.
Schmidt, Bernd
Heydenreich, Matthias
Burgos, Viviana
|
| Título |
Drimane Sesquiterpene Aldehydes Control Candida Yeast Isolated from Candidemia in Chilean Patients
|
| Editorial |
MDPI
|
| Revista |
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
|
| Lenguaje |
en
|
| 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 alpha,beta-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 mu g/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 mu g/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.
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| Tipo de Recurso |
artículo original
|
| Description |
This research was funded by ANID of the Chilean government under Fondecyt 1220831 granted to C.P. MALDI-TOF-MS analyses were developed using equipment funded by CONICYT/Chile through the project Fondequip EQM160054 2016.
Esta investigación fue financiada por la ANID del gobierno de Chile bajo el Fondecyt 1220831 otorgado a C.P. Los análisis MALDI-TOF-MS se desarrollaron utilizando equipos financiados por CONICYT/Chile a través del proyecto Fondequip EQM160054 2016.
|
| doi |
10.3390/ijms231911753
|
| Formato Recurso |
PDF
|
| Palabras Claves |
drimane sesquiterpenoids
Drimys winteri
isotadeonal
winterdial
Candida yeast
lanosterol 14-alpha-demethylase
molecular dynamics
TRP CHANNEL ACTIVATION
ALBICANS
MECHANISM
|
| Ubicación del archivo | |
| Categoría OCDE |
Bioquímica y Biología Molecular
Química
Multidisciplinar
|
| Materias |
driman sesquiterpenoides
Drimys winteri
isotadeonal
winterdial
levadura Candida
lanosterol 14-alfa-desmetilasa
dinámica molecular
ACTIVACIÓN DEL CANAL TRP
ALBICANOS
MECANISMO
|
| Título de la cita (Recomendado-único) |
Drimane Sesquiterpene Aldehydes Control Candida Yeast Isolated from Candidemia in Chilean Patients
|
| Identificador del recurso (Mandatado-único) |
artículo original
|
| Versión del recurso (Recomendado-único) |
version publicada
|
| License |
CC BY 4.0
|
| Condición de la licencia (Recomendado-repetible) |
CC BY 4.0
|
| Derechos de acceso |
acceso abierto
|
| Access Rights |
acceso abierto
|
| Referencia del Financiador (Mandatado si es aplicable-repetible) |
ANID-FONDECYT 1220831
CONICYT-FONDEQUIP EQM160054
ANID FONDECYT 1220831
|
| Id de Web of Science |
WOS:000867774900001
|
cienciaabierta.ufro.cl
ciencia.abierta@ufrontera.cl