Structure-Activity Relationship Study on Col-003, a Protein-Protein Interaction Inhibitor between Collagen and Hsp47.
Chem Pharm Bull (Tokyo)
; 68(3): 220-226, 2020 Mar 01.
Article
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| MEDLINE
| ID: mdl-31582590
ABSTRACT
This study demonstrates the structure-activity relationship of Col-003, a potent collagen-heat-shock protein 47 (Hsp47) interaction inhibitor. Col-003 analogues were successfully synthesized by Pd(0)-catalyzed cross-coupling reactions of 5-bromosalicylaldehyde derivatives with alkyl-metal species, and the inhibitory activities of the synthetic analogues were evaluated using surface plasmon resonance analysis (BIAcore). We succeeded in discovering two potent inhibitors that showed 85 and 81% inhibition at a concentration of 1.9 µM against the collagen-Hsp47 interaction. This indicates that elongation of an alkyl linker between two aromatic rings could considerably improve inhibitory activity due to the adjustment of a pendant phenyl moiety to an appropriate position, in addition to the hydrophobic interaction with an alkyl linker moiety.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Colágeno
/
Aldehídos
/
Proteínas del Choque Térmico HSP47
/
Bibliotecas de Moléculas Pequeñas
Límite:
Animals
Idioma:
En
Año:
2020
Tipo del documento:
Article