Interrelations between anti-tumour activity, DNA breakage, and DNA binding kinetics for 9-aminoacridinecarboxamide anti-tumour agents.
For a series of 9-aminoacridinecarboxamides, anti-tumour activity in vivo and cytotoxicity in vitro are correlated directly with the ability of the compounds to cause DNA single-strand breaks and with their DNA-dissociation mechanisms and residence times. It is suggested that one important consequence of long DNA residence times may be an enhanced ability to cause DNA strand breaks by a non-oxidative mechanism.
Denny
W A
WA
Cancer Research Laboratory, University of Auckland School of Medicine, New Zealand.
Roos
I A
IA
Wakelin
L P
LP
D000609:Aminoacridines / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D006860:Hydrogen Bonding; D007700:Kinetics; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000609:Aminoacridines; D000970:Antineoplastic Agents; D004247:DNA