A highly HDAC6-selective inhibitor acts as a fluorescent probe
Journal
Organic and Biomolecular Chemistry
Journal Volume
16
Journal Issue
42
Pages
7820
Date Issued
2018
Author(s)
Ho, Yi-Hsun
Wang, Kuang-Jui
Hung, Pei-Yun
Liu, Jia-Rong
Fung, Sheang-Tze
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.
SDGs
Type
journal article