A sub-milligram-synthesis protocol for in vitro screening of HDAC11 inhibitors

Bioorg Med Chem Lett. 2016 May 15;26(10):2434-2437. doi: 10.1016/j.bmcl.2016.03.116. Epub 2016 Apr 1.

Abstract

This work demonstrated the high efficiency of a sub-milligram-synthesis based medicinal chemistry method. Totally 72 compounds, consisting a tri-substituted pyrrolidine core, were prepared. Around 0.1mg of each compound was solid-phase synthesized. Based on the additive property of UV absorptions of unconjugated chromophores of a molecule, these compounds were quantified by UV measurement. A hit, whose IC50 value was 1.2μM in HDAC11 inhibition assays, highlights the applicability of the approach reported here in future optimization works.

Keywords: HDAC11; Solid phase synthesis; Sub-milligram-synthesis; UV quantification; Unconjugated chromophore.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Evaluation, Preclinical / methods*
  • Histone Deacetylase Inhibitors / chemical synthesis*
  • Histone Deacetylase Inhibitors / pharmacology*
  • Histone Deacetylases / chemistry
  • Histone Deacetylases / metabolism*
  • Inhibitory Concentration 50
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Sf9 Cells
  • Solid-Phase Synthesis Techniques
  • Spectrophotometry, Ultraviolet
  • Structure-Activity Relationship

Substances

  • Histone Deacetylase Inhibitors
  • HDAC11 protein, human
  • Histone Deacetylases