[Quenching of ethidium-DNA fluorescence by novel acridines with antitumor activities]

In order to elucidate the relationships between the antitumor activity and the molecular structure of novel acridine derivatives (1a-f, and 2a-e in Chart 1) the DNA-binding properties (intercalation) of the derivatives were examined by the quenching in fluorescence of an ethidium-DNA complex, which may be caused by the displacement of DNA-bound ethidium by a second DNA-binding ligand, acridines. The concentration (C50 value) of the acridine necessary to reduce the initial fluorescence of DNA-bound ethidium by 50% showed a good correlation with their antitumor activities. The fluorescence quenching of the acridines was examined using 4'-(9-acridinylamino)- methanesulfonanilide (amsacrine, AMSA) as a typical standard of the second DNA-bound ligand, and calf thymus DNA with an apparent site size of two base pairs.