title: Electron donor properties of the antitumour drug amsacrine as studied by fluorescence quenching of DNA-bound ethidium.
abstract: The effect of the antitumour acridine derivative amsacrine [4'-(9-acridinylamino)methanesulphon-m-anisidide] on the fluorescence lifetime of DNA-bound ethidium has been investigated using a synchronously pumped cavity dumped dye laser producing picosecond pulses for sample excitation and a time-correlated single photon counting detection system. As the proportion of DNA-bound amsacrine on the synthetic DNA polymer poly[deoxyadenylic-thymidylic acid] is increased, the fluorescence decay curve of ethidium can be accurately resolved into two exponential components. The short lifetime component, whose proportion increases with increasing proportions of DNA-bound amsacrine, has a lifetime of between 3 and 4 ns, significantly longer than that of ethidium in aqueous solution (1.63 ns). The magnitude of the long lifetime component decreases from 25.4 to 14 ns with increasing proportions of bound amsacrine. It is concluded that a new fluorescence state of ethidium (lifetime 3-4 ns) is present, probably resulting from reversible electron transfer between ethidium and amsacrine. The ability of various 9-anilinoacridine derivatives to quench the fluorescence of DNA-bound ethidium appears to be related to the electron donor properties of the substituents on the anilino ring, as well as to experimental antitumour activity. The electron donor properties of DNA-bound amsacrine may therefore be relevant to its antitumour action.
mesh_terms: D000166:Acridines / Q000494:pharmacology; D000677:Amsacrine / Q000494:pharmacology*; D004247:DNA; D003864:Depression, Chemical; D004563:Electrochemistry; D004583:Electrons; D004996:Ethidium; D005453:Fluorescence; D005470:Fluorometry; D011067:Poly dA-dT
chemical_list: D000166:Acridines; D000677:Amsacrine; D011067:Poly dA-dT; D004247:DNA; D004996:Ethidium