Piperazine propanol derivative as a novel antifungal targeting 1,3-beta-D-glucan synthase.
Biol Pharm Bull
; 28(11): 2138-41, 2005 Nov.
Article
en En
| MEDLINE
| ID: mdl-16272705
ABSTRACT
1,3-beta-D-Glucan synthase, which synthesizes a main component of fungal cell wall, is one of the promising targets for antifungal agents. In order to identify novel chemical classes of 1,3-beta-D-glucan synthase inhibitors, we screened a chemical library monitoring inhibition of the Candida albicans 1,3-beta-D-glucan synthase activity. The piperazine propanol derivative GSI578 [(2,6-difluoro-phenyl)-carbamic acid 3-(4-benzothiazol-2-yl-piperazine-1-yl)-propyl ester] was identified as a potent inhibitor against 1,3-beta-D-glucan synthase with an IC50 value of 0.16 microM. GSI578 exhibited in vitro antifungal activity against pathogenic fungi including C. albicans and Aspergillus fumigatus. Temperature-sensitive mutations of the FKS1 gene in the Deltafks2 background of Saccharomyces cerevisiae, where FKS1 and FKS2 encode putative catalytic subunits of 1,3-beta-D-glucan synthase, altered sensitivity to GSI578. This suggests that the antifungal activity of the piperazine propanol derivative has an effect on 1,3-beta-D-glucan synthase inhibition. Results of our initial evaluation suggest that the piperazine propanol derivative is a novel chemical structure of the class of antifungals which inhibit fungal cell growth by inhibiting fungal 1,3-beta-D-glucan synthase.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Piperazinas
/
Saccharomyces cerevisiae
/
Inhibidores Enzimáticos
/
Ésteres
/
Glucosiltransferasas
/
Antifúngicos
Idioma:
En
Revista:
Biol Pharm Bull
Asunto de la revista:
BIOQUIMICA
/
FARMACOLOGIA
Año:
2005
Tipo del documento:
Article
País de afiliación:
Japón