title: Inhibition of mammalian topoisomerase I by 1-nitro-9-aminoacridines. Dependence on thiol activation.
abstract: The cytotoxic activity, susceptibility to thiol activation and ability of eight 1-nitroacridine derivatives to stabilize the topoisomerase I-DNA cleavable complex, were compared. Among the acridines tested three compounds exhibited high ability to stabilize the cleavable complex. This ability was correlated with susceptibility to thiol activation as well as with cytotoxic activity. Our results suggest that 1-nitroacridine-DNA adducts interfering with topoisomerase I action may contribute to the lethal effects of some 1-nitroacridine derivatives.
authors.affiliation: Department of General Chemistry, Institute of Physiology and Biochemistry, Medical University in Lódź, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Ciesielska
authors.forename: E
authors.initials: E
authors.lastname: Pastwa
authors.forename: L
authors.initials: L
authors.lastname: Szmigiero
mesh_terms: D000609:Aminoacridines / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D018736:DNA Adducts / Q000378:metabolism; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004278:DNA, Superhelical / Q000378:metabolism; D004229:Dithiothreitol / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004795:Enzyme Stability / Q000187:drug effects; D066298:In Vitro Techniques; D007939:Leukemia L1210 / Q000201:enzymology; D051379:Mice; D059004:Topoisomerase I Inhibitors
chemical_list: D000609:Aminoacridines; D018736:DNA Adducts; D004278:DNA, Superhelical; D004791:Enzyme Inhibitors; D059004:Topoisomerase I Inhibitors; D004264:DNA Topoisomerases, Type I; D004229:Dithiothreitol