New hemisynthetic derivatives of sphaeropsidin phytotoxins triggering severe endoplasmic reticulum swelling in cancer cells.
Sci Rep
; 14(1): 14674, 2024 06 25.
Article
de En
| MEDLINE
| ID: mdl-38918539
ABSTRACT
Sphaeropsidins are iso-pimarane diterpenes produced by phytopathogenic fungi that display promising anticancer activities. Sphaeropsidin A, in particular, has been shown to counteract regulatory volume increase, a process used by cancer cells to avoid apoptosis. This study reports the hemi-synthesis of new lipophilic derivatives obtained by modifications of the C15,C16-alkene moiety. Several of these compounds triggered severe ER swelling associated with strong proteasomal inhibition and consequently cell death, a feature that was not observed with respect to mode of action of the natural product. Significantly, an analysis from the National Cancer Institute sixty cell line testing did not reveal any correlations between the most potent derivative and any other compound in the database, except at high concentrations (LC50). This study led to the discovery of a new set of sphaeropsidin derivatives that may be exploited as potential anti-cancer agents, notably due to their maintained activity towards multidrug resistant models.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Réticulum endoplasmique
Limites:
Humans
Langue:
En
Journal:
Sci Rep
/
Sci. rep. (Nat. Publ. Group)
/
Scientific reports (Nature Publishing Group)
Année:
2024
Type de document:
Article
Pays d'affiliation:
Belgique
Pays de publication:
Royaume-Uni