Multicomponent Synthesis and Binding Mode of Imidazo[1,2- a]pyridine-Capped Selective HDAC6 Inhibitors

Org Lett. 2018 Jun 1;20(11):3255-3258. doi: 10.1021/acs.orglett.8b01118. Epub 2018 May 23.

Abstract

The multicomponent synthesis of a mini-library of histone deacetylase inhibitors with imidazo[1,2- a]pyridine-based cap groups is presented. The biological evaluation led to the discovery of the hit compound MAIP-032 as a selective HDAC6 inhibitor with promising anticancer activity. The X-ray structure of catalytic domain 2 from Danio rerio HDAC6 complexed with MAIP-032 revealed a monodentate zinc-binding mode.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Histone Deacetylase 6 / antagonists & inhibitors*
  • Histone Deacetylase Inhibitors
  • Imidazoles
  • Molecular Structure
  • Pyridines / chemistry*
  • Zebrafish
  • Zebrafish Proteins / antagonists & inhibitors*

Substances

  • Histone Deacetylase Inhibitors
  • Imidazoles
  • Pyridines
  • Zebrafish Proteins
  • HDAC6 protein, zebrafish
  • Histone Deacetylase 6