Efficient breakage of DNA apurinic sites by the indoleamine related 9-amino-ellipticine.
The aromatic amine, 9-NH2-ellipticine, is a synthetic DNA intercalating derivative of the antitumor agent ellipticine, which breaks circular DNA containing apurinic sites. This breakage is inhibited when the apurinic (AP) sites are reduced. The concentration of 9-NH2-ellipticine required to get a significant effect (0.1 microM) is the lowest known among chemicals which induce the same breakage reaction. Comparison with the action of structurally related amines shows that the amino-indole structure is specific for AP sites. The ability of ellipticine derivatives to induce breakage in DNA containing apurinic sites is related to the nucleophile substituent in position 9. Two ellipticine derivatives with known antitumor activity, BD 40 and 9-OH-ellipticine, were able to break purified DNA at apurinic sites.
D000470:Alkaloids / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D004247:DNA / Q000378:metabolism*; D004269:DNA, Bacterial / Q000378:metabolism; D004270:DNA, Circular / Q000378:metabolism; D004611:Ellipticines / Q000494:pharmacology*; D004926:Escherichia coli / Q000235:genetics; D004996:Ethidium; D005453:Fluorescence; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009691:Nucleic Acid Denaturation; D010084:Oxidation-Reduction / Q000187:drug effects; D012995:Solubility; D013329:Structure-Activity Relationship
D000470:Alkaloids; D004269:DNA, Bacterial; D004270:DNA, Circular; D004611:Ellipticines; C038373:9-aminoellipticine; D004247:DNA; D004996:Ethidium