ZFIN ID: ZDB-PUB-181119-5
Highly fluorescent and HDAC6 selective scriptaid analogues
Fleming, C.L., Natoli, A., Schreuders, J., Devlin, M., Yoganantharajah, P., Gibert, Y., Leslie, K.G., New, E.J., Ashton, T.D., Pfeffer, F.M.
Date: 2018
Source: European Journal of Medicinal Chemistry   162: 321-333 (Journal)
Registered Authors: Gibert, Yann
Keywords: 4MS, Fluorescence, HDAC, Imaging, Naphthalimide, Scriptaid, Zebrafish
MeSH Terms:
  • Animals
  • Blood Vessels/diagnostic imaging
  • Blood Vessels/metabolism
  • Cytoplasm/metabolism
  • Diagnostic Imaging/methods
  • Fluorescence
  • Histone Deacetylase 6/antagonists & inhibitors*
  • Histone Deacetylase Inhibitors/pharmacokinetics
  • Histone Deacetylase Inhibitors/therapeutic use
  • Hydroxylamines/chemical synthesis
  • Hydroxylamines/chemistry*
  • Hydroxylamines/pharmacokinetics
  • Quinolines/chemical synthesis
  • Quinolines/chemistry*
  • Quinolines/pharmacokinetics
  • Zebrafish/metabolism
PubMed: 30448419 Full text @ Eur. J. Med. Chem.
ABSTRACT
Fluorescent scriptaid analogues with excellent HDAC6 selectivity (HDAC1/6 > 500) and potency (HDAC6 IC50 < 5 nM) have been synthesised and evaluated. The highly fluorescent nature of the compounds (up to ΦF = 0.83 in DMSO and 0.38 in aqueous buffer) makes them ideally suited for cellular imaging and visualisation of their cytoplasmic localisation was readily accomplished. Whole organism imaging in zebrafish confirmed both the vascular localisation of the new inhibitors and the impact of HDAC6 inhibition on in vivo development.
ADDITIONAL INFORMATION No data available