Interaction of the antitumour drug 4'-(9-acridinylamino)-methanesulfon-m-anisidine.HCl (m-AMSA) with nucleic acids.
The interaction of AMSA with nucleic acids was studied by several techniques. Melting temperature and CD studies equally suggest that AMSA-binding is interfering with the secondary structure of DNA. An overlap by two mechanism of binding seems to exist. Based on the CD measurements at low drug concentration intercalation is the most likely way of binding. At higher drug concentration stacking interaction predominates leading to cooperativity and formation of oriented sheets of aromatic ring-systems as reflected in the optical activity induced in the metachromatic band of the achiral drug. No base-pair specificity could be confirmed; however, a high affinity of AMSA to poly(A) chains was demonstrated. The CD measurements did not indicate any significant interaction with RNA. The selectivity of the AMSA-DNA interaction can be regarded as an important argument in favour of the role of this interaction in the anti-tumour effect of the drug.
D000609:Aminoacridines / Q000378:metabolism*; D000677:Amsacrine; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism; D002942:Circular Dichroism; D004247:DNA / Q000378:metabolism*; D006358:Hot Temperature; D066298:In Vitro Techniques; D007364:Intercalating Agents / Q000378:metabolism; D009691:Nucleic Acid Denaturation; D012313:RNA / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013057:Spectrum Analysis
D000609:Aminoacridines; D000970:Antineoplastic Agents; D007364:Intercalating Agents; D000677:Amsacrine; D012313:RNA; D004247:DNA