Hypoxia-driven elimination of thiopurines from their nitrobenzyl prodrugs.
A novel bioreductive prodrug of 6-thioguanine, 2-amino-6-[2-(4-nitrophenyl)prop-2-ylsulfanyl]-9H-purine, containing a gem-dimethyl thioether linkage, was synthesised and compared with its unsubstituted analogue. In A549 whole cell experiments hypoxia selective release of 6-thioguanine was observed with the substituted prodrug only.
Thomson
Peter
P
University of Oxford, Gray Cancer Institute, Mount Vernon Hospital, Northwood, Middlesex HA6 2JR, UK. thomson@gci.ac.uk
Naylor
Matthew A
MA
Stratford
Michael R L
MR
Lewis
Gemma
G
Hill
Sally
S
Patel
Kantilal B
KB
Wardman
Peter
P
Davis
Peter D
PD
D015687:Cell Hypoxia; D002460:Cell Line; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D011355:Prodrugs / Q000737:chemistry*; D011687:Purines / Q000737:chemistry*
D011355:Prodrugs; D011687:Purines