Mapping the ATP-binding domain of DNA-dependent protein kinase (DNA-PK) with coumarin- and isocoumarin-derived inhibitors.
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.
Payne
Sara L
SL
Northern Institute for Cancer Research, School of Chemistry, Newcastle University, Newcastle Upon Tyne, UK.
Rodriguez-Aristegui
Sonsoles
S
Bardos
Julia
J
Cano
Céline
C
Golding
Bernard T
BT
Hardcastle
Ian R
IR
Peacock
Marcus
M
Parveen
Nahida
N
Griffin
Roger J
RJ
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000970:Antineoplastic Agents; D001665:Binding Sites; D002867:Chromones; D003374:Coumarins / Q000037:antagonists & inhibitors*; D051747:DNA-Activated Protein Kinase / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D049934:Isocoumarins / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D002867:Chromones; D003374:Coumarins; D049934:Isocoumarins; D000255:Adenosine Triphosphate; C030123:coumarin; D051747:DNA-Activated Protein Kinase