[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.
Kimura
M
M
Department of Pharmacy, Kyoto University Hospital Faculty of Medicine, Japan.
D000166:Acridines / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004247:DNA; D004996:Ethidium; D005453:Fluorescence; D007364:Intercalating Agents; D007939:Leukemia L1210 / Q000188:drug therapy / Q000473:pathology; D008297:Male; D051379:Mice; D013329:Structure-Activity Relationship
D000166:Acridines; D000970:Antineoplastic Agents; D007364:Intercalating Agents; D004247:DNA; D004996:Ethidium