2. Academic Validation
  3. Highly fluorescent and HDAC6 selective scriptaid analogues

Highly fluorescent and HDAC6 selective scriptaid analogues

  • Eur J Med Chem. 2019 Jan 15:162:321-333. doi: 10.1016/j.ejmech.2018.11.020.
Cassandra L Fleming 1,  Anthony Natoli 2,  Jeannette Schreuders 2,  Mark Devlin 2,  Prusothman Yoganantharajah 3,  Yann Gibert 3,  Kathryn G Leslie 4,  Elizabeth J New 4,  Trent D Ashton 5,  Frederick M Pfeffer 6
Affiliations

Affiliations

  • 1 School of Life & Environmental Sciences, Deakin University, Waurn Ponds, Victoria, 3216, Australia.
  • 2 Peter MacCallum Cancer Centre, Parkville, Melbourne, Victoria, 3000, Australia.
  • 3 School of Medicine, Deakin University, Waurn Ponds, Victoria, 3216, Australia.
  • 4 School of Chemistry, The University of Sydney, Sydney, New South Wales, 2006, Australia.
  • 5 School of Life & Environmental Sciences, Deakin University, Waurn Ponds, Victoria, 3216, Australia; Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, 3010, Australia.
  • 6 School of Life & Environmental Sciences, Deakin University, Waurn Ponds, Victoria, 3216, Australia. Electronic address: fred.pfeffer@deakin.edu.au.
PMID: 30448419 DOI: 10.1016/j.ejmech.2018.11.020
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.

Keywords

4MS; Fluorescence; HDAC; Imaging; Naphthalimide; Scriptaid; Zebrafish.

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