Identification of new γ-hydroxybutenolides that preferentially inhibit the activity of mPGES-1.
Bioorg Med Chem
; 20(16): 5012-6, 2012 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-22795900
ABSTRACT
Microsomal prostaglandin E(2) synthase-1 (mPGES-1) has been recognized as novel, promising drug target for anti-inflammatory and anticancer drugs. mPGES-1 catalyzes the synthesis of the inducible prostaglandin E(2) in response to pro-inflammatory stimuli, rendering this enzyme extremely interesting in drug discovery process owing to the drastic reduction of the severe side effects typical for traditional non-steroidal anti-inflammatory drugs. In the course of our investigations focused on this topic, we identified two interesting molecules bearing the γ-hydroxybutenolide scaffold which potently inhibit the activity of mPGES-1. Notably, the lead compound 2c that inhibited mPGES-1 with IC(50) = 0.9 µM, did not affect other related enzymes within the arachidonic acid cascade.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
4-Butirolactona
/
Oxirredutases Intramoleculares
/
Inibidores Enzimáticos
Tipo de estudo:
Diagnostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article