A highly HDAC6-selective inhibitor acts as a fluorescent probe.
Org Biomol Chem
; 16(42): 7820-7832, 2018 10 31.
Article
em En
| MEDLINE
| ID: mdl-30168823
ABSTRACT
HDAC6 receives great attention because of its therapeutic potential for the treatment of various diseases. Selective fluorescence imaging for HDAC6 is important for its pathological and biological studies. However, specific detection of HDAC6 by using a fluorescent small molecule probe remains a great challenge. Herein, a series of fluorescent HDAC6-selective inhibitors incorporating a naphthalimide skeleton were designed and synthesized. A structure-activity relationship study identified that compound JW-1 had the greatest inhibitory activity and superior specificity against HDAC6. JW-1 could substantially increase α-tubulin acetylation and was active against a panel of six cancer cell lines. Photophysical characterization and cellular imaging of MDA-MB-231 cells demonstrated that JW-1 is a highly fluorescent, cell penetrable, small-molecule inhibitor of HDAC6 that can be used for the detection of HDAC6 in complex cellular environments.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Inibidores de Histona Desacetilases
/
Corantes Fluorescentes
/
Desacetilase 6 de Histona
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article