A minimally-masked inactive prodrug of panobinostat that is bioorthogonally activated by gold chemistry

Bioorg Med Chem. 2021 Jul 1:41:116217. doi: 10.1016/j.bmc.2021.116217. Epub 2021 May 15.

Abstract

The recent incorporation of Au chemistry in the bioorthogonal toolbox has opened up new opportunities to deliver biologically independent reactions in living environments. Herein we report that the O-propargylation of the hydroxamate group of the potent HDAC inhibitor panobinostat leads to a vast reduction of its anticancer properties (>500-fold). We also show that this novel prodrug is converted back into panobinostat in the presence of Au catalysts in vitro and in cell culture.

Keywords: Anticancer therapies; Bioorthogonal catalysis; Gold nanoparticles; HDAC inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Catalysis
  • Cell Line, Tumor
  • Cell Survival
  • Gold
  • Humans
  • Panobinostat / chemistry*
  • Panobinostat / pharmacology*
  • Prodrugs / chemistry*
  • Prodrugs / pharmacology*

Substances

  • Antineoplastic Agents
  • Prodrugs
  • Gold
  • Panobinostat