Inhibitors of Sir2: evaluation of splitomicin analogues.
J Med Chem
; 47(10): 2635-44, 2004 May 06.
Article
em En
| MEDLINE
| ID: mdl-15115404
ABSTRACT
Splitomicin (1) and 41 analogues were prepared and evaluated in cell-based Sir2 inhibition and toxicity assays and an in vitro Sir2 inhibition assay. Lactone ring or naphthalene (positions 7-9) substituents decrease activity, but other naphthalene substitutions (positions 5 and 6) are well-tolerated. The hydrolytically unstable aromatic lactone is important for activity. Lactone hydrolysis rates were used as a measure of reactivity; hydrolysis rates correlate with inhibitory activity. The most potent Sir2 inhibitors were structurally similar to and had hydrolysis rates similar to 1.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Pironas
/
Sirtuínas
/
Naftalenos
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article