Effect of C2/C3-endo unsaturation on the cytotoxicity and DNA-binding reactivity of pyrrolo[2,1-c][1,4]benzodiazepines.
A series of novel C2,C3-endo unsaturated pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) has been synthesised via cleavage of the N10-Alloc protecting group from appropriate precursors. Biophysical and biological evaluations show that the presence of C2/C3-endo unsaturation in the PBD C-ring enhances both DNA-binding reactivity and in vitro cytotoxic potency.
Gregson
S J
SJ
CRC Gene Targeted Drug Design Research Group, School of Pharmacy and Biomedical Science, University of Portsmouth, Hants, UK.
Howard
P W
PW
Barcella
S
S
Nakamya
A
A
Jenkins
T C
TC
Kelland
L R
LR
Thurston
D E
DE
D000876:Anthramycin / Q000737:chemistry; D000903:Antibiotics, Antineoplastic / Q000737:chemistry* / Q000378:metabolism; D001569:Benzodiazepines / Q000737:chemistry* / Q000378:metabolism; D002625:Chemistry, Organic; D004247:DNA / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D015394:Molecular Structure; D055601:Organic Chemistry Phenomena; D010051:Ovarian Neoplasms; D011758:Pyrroles / Q000737:chemistry* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D011758:Pyrroles; D000876:Anthramycin; D001569:Benzodiazepines; D004247:DNA