Existence of an extended series of antitumor compounds which bind to deoxyribonucleic acid by nonintercalative means.

Abstract

Viscometric titrations of bacteriophage PM2 closed circular DNA, in addition to spectrophotometric and fluorometric methods, were used to investigate the mode of DNA binding of a number of antitrypanosomal and antitumor compounds. Several classes of compounds were identified which failed to unwind PM2 DNA, which appeared to have a large DNA binding site of at least 4 base pairs and which often showed considerable selectivity of binding to poly[d(AT)] as opposed to poly[d(GC)]. The classes included the antiviral antibiotics distamycin and netropsin, bisamidines such as the trypanocidal drug berenil, phthalanilide bisamidines, aromatic bis(guanylhydrazones), and the bisquaternary ammonium heterocycles. It is proposed that the compounds all bind in the minor groove of the DNA double helix.