A molecular modeling study of B-DNA-intercalation complexes with amsacrine and related 9-anilino-acridines

Computer molecular modeling studies of some complexes of amsacrine-derivatives with B-DNA-hexanucleotides were performed to shed new light on the DNA-binding mode of these drugs. The studies are based on routine methods, as are the semiempirical calculations, conformational analyses of the ligands, interaction field analyses, force field and molecular dynamics simulations of ligand/base paired DNA-complexes. The predictions suggest that the tested 9-anilino-acridines 1, 3 and 4 bind by intercalation to the base-paired oligonucleotides. Depending on the substitution pattern of the tested 9-anilino-acridine-series compounds, some distinct binding modes and base sequence selectivities were observed.