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A wide range of aromatic compounds has been shown to amplify phleomycin-induced cell killing in Escherichia coli. They include acridines, acridinium chlorides, dihydroanthracenes, anthracenes, dianthracenes, phenanthridinium salts, phenazinium chlorides, phenoxazones, triphenyl methane dyes, benzoquinolizinium chloride, diphenylmethane derivatives, stilbene and diphenyl derivatives. Low concentrations of these amplifiers also amplified the DNA breakage and degradation effects of phleomycin. The minimum structural specification for activity as an amplifying agent is suggested. A representative sample of compounds effective as amplifiers of phleomycin also amplified the antibiotic effects of bleomycins B4 and B6. The amplifiers described are known to vary in their ability to penetrate and accumulate in different organisms or tissues. This suggests the possibility of developing a series of antibiotic regimes using these amplifiers (or the large number of derivative compounds also likely to be active) where the therapeutic index is determined by the properties of the amplifier chosen rather than of the phleomycin or the bleomycin.

Amplifications of phleomycin and bleomycin-induced antibiotic activity in Escherichia coli by aromatic cationic compounds.