Squalestatin is an inhibitor of carotenoid biosynthesis in Plasmodium falciparum.
Antimicrob Agents Chemother
; 59(6): 3180-8, 2015.
Article
en En
| MEDLINE
| ID: mdl-25779575
ABSTRACT
The increasing resistance of malaria parasites to almost all available drugs calls for the characterization of novel targets and the identification of new compounds. Carotenoids are polyisoprenoids from plants, algae, and some bacteria, and they are biosynthesized by Plasmodium falciparum but not by mammalian cells. Biochemical and reverse genetics approaches were applied to demonstrate that phytoene synthase (PSY) is a key enzyme for carotenoid biosynthesis in P. falciparum and is essential for intraerythrocytic growth. The known PSY inhibitor squalestatin reduces biosynthesis of phytoene and kills parasites during the intraerythrocytic cycle. PSY-overexpressing parasites showed increased biosynthesis of phytoene and its derived product phytofluene and presented a squalestatin-resistant phenotype, suggesting that this enzyme is the primary target of action of this drug in the parasite.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Plasmodium falciparum
/
Carotenoides
/
Compuestos Bicíclicos Heterocíclicos con Puentes
/
Antimaláricos
Idioma:
En
Revista:
Antimicrob Agents Chemother
Año:
2015
Tipo del documento:
Article
País de afiliación:
Brasil