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

Sara L Payne; Sonsoles Rodriguez-Aristegui; Julia Bardos; Céline Cano; Bernard T Golding; Ian R Hardcastle; Marcus Peacock; Nahida Parveen; Roger J Griffin

doi:10.1016/j.bmcl.2010.04.102

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.

Authors

Sara L Payne¹, Sonsoles Rodriguez-Aristegui, Julia Bardos, Céline Cano, Bernard T Golding, Ian R Hardcastle, Marcus Peacock, Nahida Parveen, Roger J Griffin

Affiliation

¹ Northern Institute for Cancer Research, School of Chemistry, Newcastle University, Newcastle Upon Tyne, UK.

PMID: 20472428
DOI: 10.1016/j.bmcl.2010.04.102

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

Grants and funding

Cancer Research UK/United Kingdom