Comparison of the interaction of antineoplastic aminoanthraquinone analogs with DNA using competitive fluorescence...

1,4-dihydroxy-5-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]-9,10-anthracenedione one (NSC 287836) and 1,4-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]-9,10-anthracenedione diacetate (NSC 287513) have shown activity against solid tumors and are now in Phase I clinical trials. Fluorescence polarization was used to determine the extent of inhibition of the binding of acridine orange to DNA (Richardson, Boboz, Holland, Res. Comm. Chem. Pathol. Pharmac. 27, 497, 1980). Displacement of 50% of acridine orange from calf thymus DNA was obtained with 0.18 micro M of NSC 287836 while 0.52 micro M of NSC 287513 was needed to displace an equivalent amount of acridine orange. NSC 287513 showed preference for polynucleotides of high adenine + thymine content while NSC 287836 did not. Analogs lacking both hydroxyethylaminoethyl-amino side chains did not displace acridine orange.