Development of Class I Selective Histone Deacetylase Inhibitors for Cellular Imaging Studies.

Abstract

Histone deacetylase (HDAC) has arisen as a novel molecular target in playing a preventative role several diseases such as cancer, oxidative stress and inflammation. Despite efforts made to develop potent HDAC inhibitors, further research is required for the development of class I selective HDAC inhibitors that exhibit innate fluorescent properties, as limited techniques are available for the visualisation of class I selective HDAC inhibitiors. Hence, this study aimed to develop highly fluorescent class I selective HDAC inhibitors that have potential access to the nucleus. This was to be achieved by merging highly fluorescent 4-amino-1,8-naphthalimde derivatives into the pharmacophore of a previously reported class I selective HDAC inhibitor. Furthermore, this study also identified amino moieties that could contribute to the increase of fluorescent quantum yields in aqueous solution so that these fluorescent HDAC inhibitor may find application in cellular imaging studies.