Design and synthesis of novel pyrrolobenzodiazepine (PBD) prodrugs for ADEPT and GDEPT.
Three N10-(4-nitrobenzyl)carbamate-protected PBD prodrugs (9a, 9b and 15) have been synthesized and evaluated for potential use in nitroreductase-based ADEPT and GDEPT therapies. An approximately 100-fold activation was observed for the DC-81 prodrug 9a.
Sagnou
M J
MJ
CRC Gene Targeting Drug Design Research Group, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Hants, UK.
Howard
P W
PW
Gregson
S J
SJ
Eno-Amooquaye
E
E
Burke
P J
PJ
Thurston
D E
DE
D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis / Q000494:pharmacology; D001569:Benzodiazepines / Q000138:chemical synthesis* / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020128:Inhibitory Concentration 50; D009243:NAD / Q000494:pharmacology; D009601:Nitroreductases / Q000494:pharmacology; D011355:Prodrugs / Q000138:chemical synthesis / Q000494:pharmacology; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D011355:Prodrugs; D011758:Pyrroles; D009243:NAD; D001569:Benzodiazepines; D009601:Nitroreductases