Design, synthesis, inhibitory activity, and binding mode study of novel DNA methyltransferase 1 inhibitors

Bioorg Med Chem Lett. 2010 Feb 1;20(3):1124-7. doi: 10.1016/j.bmcl.2009.12.016. Epub 2009 Dec 21.

Abstract

To identify novel non-nucleoside DNA methyltransferase (DNMT) inhibitors, we designed and synthesized a series of maleimide derivatives. Among this series, compounds 5-8 were found to be more potent DNMT1 inhibitors than RG108, a DNMT1 inhibitor reported previously by Siedlecki et al. The binding mode analysis of compound 5 is also reported.

Publication types

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

MeSH terms

  • Crystallography, X-Ray
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases / antagonists & inhibitors*
  • DNA (Cytosine-5-)-Methyltransferases / metabolism*
  • Drug Design*
  • Humans
  • Indoles / chemistry
  • Indoles / metabolism
  • Maleimides / chemical synthesis*
  • Maleimides / metabolism*
  • Phthalimides
  • Propionates / chemistry
  • Propionates / metabolism
  • Protein Binding / physiology
  • Tryptophan / analogs & derivatives

Substances

  • Indoles
  • Maleimides
  • Phthalimides
  • Propionates
  • RG108
  • Tryptophan
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases
  • DNMT1 protein, human