Discovery of novel 9H-purin derivatives as dual inhibitors of HDAC1 and CDK2

Bioorg Med Chem Lett. 2019 Aug 15;29(16):2136-2140. doi: 10.1016/j.bmcl.2019.06.059. Epub 2019 Jun 29.

Abstract

HDAC and CDK inhibitors have been demonstrated to be synergistically in suppressing cancer cell proliferation and inducing apoptosis. In this work, we incorporated the pharmacophore groups of HDACs and CDKs inhibitors into one molecule to design and synthesize a series of purin derivatives as HDAC/CDK dual inhibitors. The lead compound 6d, showing good HDAC1 and CDK2 inhibitory activity with IC50 values of 5.8 and 56 nM, respectively, exhibited attractive potency against several cancer cell lines in vitro. This work may lead to the discovery of a novel scaffold andpotentialdual HDAC/CDK inhibitors.

Keywords: Antitumor; CDKs; Dual inhibitors; HDACs; Purin.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Design
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylase Inhibitors / therapeutic use*
  • Humans
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Histone Deacetylase Inhibitors