Nonintercalative DNA-binding antitumour compounds

Summary A family of compounds which appear to bind reversibly to double stranded DNA without intercalation between DNA base pairs has been defined. Methods are described by which this non-intercalative binding can be characterised using ultraviolet spectrometry, fluorimetry with ethidium as a probe, viscometry and other hydrodynamic techniques, circular dichroism and nuclear magnetic resonance spectrometry. Antibiotics which fall into this family include the antibiotics distamycin A, netropsin, mithramycin, chromomycin and olivomycin. Synthetic antitumour agents include diarylamidines such as berenil, phthalanilides, aromatic bisguanylhydrazones and bisquaternary ammonium heterocycles. A survey has been made of the general requirements of this family of compounds for DNA binding and biological activity. Binding of drugs to the minor groove of the DNA double helix appears to be the most likely mechanism for the antitumour action of these compounds.