Mechanism of action of dnacin B1, a new benzoquinoid antibiotic with antitumor properties.

Dnacin B1 preferentially inhibited the incorporation of [3H]thymidine into acid-insoluble fractions in Escherichia coli. At a sublethal concentration, dnacin B1 caused filamentous growth in E. coli and induced prophage lambda. The antibiotic also showed potent bactericidal activity against repair-deficient E. coli strains, such as recA, recB, and polA strains, In in vitro studies, dnacin Ba raised the melting temperatures of various double-stranded DNAs. In addition, the antibiotic showed DNA-cleaving activity against PM2 DNA in the presence of reducing agents, and the activity was suppressed by scavengers for oxygen free radicals and an iron-specific chelator, desferrioxamine E. The stimulation of the generation of superoxide radical by dnacin B1 was confirmed by measuring the reduction of neotetrazolium. Therefore, it can be presumed that the primary cellular target of dnacin B1 is DNA in susceptible cells, and the autooxidation of DNA-bound dnacin B1 causes the generation of oxygen-free radicals that result in the damage of DNA and the inhibition of its synthesis.