Design of two metal-chelating, DNA-binding models: molecular combinations of bleomycin and amsacrine anti-tumour drugs.
In the course of studies on bleomycin, we recently showed that the bithiazole ring is a poor intercalator into DNA. Therefore we have designed new models, replacing this heterocyclic moiety by an anilinoacridine ring in order to increase the affinity for DNA. This work presents results obtained for two model compounds showing (i) that the anilinoacridine nucleus leads to a good stabilization of the DNA helix, and (ii) that the presence of a bulky group near the complexing part of bleomycin is essential to the activation of molecular oxygen.
D000677:Amsacrine / Q000031:analogs & derivatives*; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D001761:Bleomycin / Q000138:chemical synthesis*; D002614:Chelating Agents / Q000138:chemical synthesis*; D003300:Copper; D004247:DNA / Q000378:metabolism*; D005609:Free Radicals; D009690:Nucleic Acid Conformation; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D002614:Chelating Agents; D005609:Free Radicals; D000677:Amsacrine; D001761:Bleomycin; D003300:Copper; D004247:DNA