Interaction of the antitumor drug 4'-(9-acridinylamino)methanesulfon-m-anisidide and related acridines with nucleic acids.

摘要: The acridine antitumor drug 49-(9-acridinylamino)methanesulfon- m -anisidide ( -AMSA), which is currently in Phase II clinical trial, known to be an inhibitor of nucleic acid synthesis. intercalative binding this native calf thymus DNA has been studied using equilibrium dialysis, spectrophotometry, and competition with ethidium. All three techniques indicate intrinsic association constant approximately 1.5 x 10 5 M -1 at ionic strength 0.01. isotherm adequately described by a neighboring-site exclusion model, indicates site size two base pairs. At elevated the depressed factor corresponds closely that predicted for monocationic ligand. Studies variety synthetic polynucleotides constants sites different sequence vary over 10-fold range. -AMSA binds heat-denatured or ribosomal RNA constants, respectively, 5- 25-fold lower than DNA. Comparable measurements have made related acridinylaminomethanesulfonanilide (AMSA) drugs simple aminoacridines; they reveal presence unsubstituted methanesulfonanilide ring does not noticeably interfere However, addition methoxy substituent 39 position ring, as -AMSA, may sterically hinder intercalation nucleus drug. activity series ligands could correlated any straightforward fashion parameters, although conspicuous ability AMSA discriminate sensitively between result efficient vivo .