Synthesis and biological evaluation of an N10-Psec substituted pyrrolo[2,1-c][1,4]benzodiazepine prodrug.
The first example of an N10-protected (e.g., Psec, 15) pyrrolo[2,1-c][1,4]benzodiazepine (PBD) analogue that retains significant cytotoxicity in a number of tumour cell lines is reported. This prototype could lead to a new generation of clinically useful N10-protected PBD prodrugs.
Berry
Jane M
JM
CRUK Gene Targeted Drug Design Research Group, Cancer Research Laboratories, School of Pharmaceutical Sciences, University of Nottingham, University Park, NG7 2RD, Nottingham, UK.
Howard
Philip W
PW
Kelland
Lloyd R
LR
Thurston
David E
DE
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001569:Benzodiazepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D011355:Prodrugs; D011758:Pyrroles; D001569:Benzodiazepines