Mapping the ATP-binding domain of DNA-dependent protein kinase (DNA-PK) with coumarin- and isocoumarin-derived inhibitors

Bioorg Med Chem Lett. 2010 Jun 15;20(12):3649-53. doi: 10.1016/j.bmcl.2010.04.102. Epub 2010 May 14.

Abstract

Replacement of the core heterocycle of a defined series of chromen-4-one DNA-PK inhibitors by the isomeric chromen-2-one (coumarin) and isochromen-1-one (isocoumarin) scaffolds was investigated. Structure-activity relationships for DNA-PK inhibition were broadly consistent, albeit with a reduction of potency compared with the parent chromenone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Antineoplastic Agents
  • Binding Sites
  • Chromones
  • Coumarins / antagonists & inhibitors*
  • DNA-Activated Protein Kinase / chemistry*
  • DNA-Activated Protein Kinase / metabolism
  • Humans
  • Inhibitory Concentration 50
  • Isocoumarins / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Chromones
  • Coumarins
  • Isocoumarins
  • Adenosine Triphosphate
  • coumarin
  • DNA-Activated Protein Kinase