Quenching of ethidium-DNA fluorescence by novel acridines with antitumor activities. II. The structure-activity relationship in acridines with fluorescence quenching of ethidium-DNA

In order to elucidate the structure-activity relationship between the antitumor activity and the molecular structure of novel DNA-intercalator acridine derivatives (1a-g and 2a-i in Chart 1), DNA-binding properties (intercalation) of these acridines were examined by quenching in the fluorescence of the ethidium-DNA complex. The mechanism of quenching is caused by the displacement of DNA-bound ethidium by a second DNA binding ligand, acridines. The concentration (C50 value) of acridine necessary to reduce the initial fluorescence of DNA-bound ethidium by 50% showed a good correlation with their antitumor activities. The quenching of fluorescence for acridines was examined using amsacrine (AMSA) as a typical standard of the second DNA-bound ligand, and calf thymus DNA with an apparent site size of two base pair. Some of the acridine derivatives showed more potent quenching of fluorescence than amsacrine (AMSA).