Structure-activity relationship studies of phenanthridine-based Bcl-XL inhibitors.
J Med Chem
; 51(21): 6699-710, 2008 Nov 13.
Article
em En
| MEDLINE
| ID: mdl-18925736
ABSTRACT
Despite their structural similarities, the natural products chelerythrine ( 5) and sanguinarine ( 6) target different binding sites on the pro-survival Bcl-X L protein. This paper details the synthesis of phenanthridine-based analogues of the natural products that were used to probe this difference in binding profiles. The inhibitory constants for these compounds were then measured in a fluorescence polarization assay against Bcl-X L and the tagged Bak-BH3 peptide. The results led to structure-activity relationship studies, which identified the structural motifs required for binding-site specificity as well as inhibitory activity. We also identified synthetic analogues of the natural products that display similar binding modes but with more potent IC 50 values.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fenantridinas
/
Proteína bcl-X
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article