title: Design and synthesis of novel pyrrolobenzodiazepine (PBD) prodrugs for ADEPT and GDEPT.
abstract: 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.
authors.affiliation: CRC Gene Targeting Drug Design Research Group, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Hants, UK.
authors.forename: M J
authors.initials: MJ
authors.lastname: Sagnou
authors.forename: P W
authors.initials: PW
authors.lastname: Howard
authors.forename: S J
authors.initials: SJ
authors.lastname: Gregson
authors.forename: E
authors.initials: E
authors.lastname: Eno-Amooquaye
authors.forename: P J
authors.initials: PJ
authors.lastname: Burke
authors.forename: D E
authors.initials: DE
authors.lastname: Thurston
mesh_terms: 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
chemical_list: D000903:Antibiotics, Antineoplastic; D011355:Prodrugs; D011758:Pyrroles; D009243:NAD; D001569:Benzodiazepines; D009601:Nitroreductases