Mechanism of action of dnacin B1, a new benzoquinoid antibiotic with antitumor properties. 1982

S Tanida, and T Hasegawa, and M Yoneda

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.

UI MeSH Term Description Entries
D011809 Quinones Hydrocarbon rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.
D004269 DNA, Bacterial Deoxyribonucleic acid that makes up the genetic material of bacteria. Bacterial DNA
D004926 Escherichia coli A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc. Alkalescens-Dispar Group,Bacillus coli,Bacterium coli,Bacterium coli commune,Diffusely Adherent Escherichia coli,E coli,EAggEC,Enteroaggregative Escherichia coli,Enterococcus coli,Diffusely Adherent E. coli,Enteroaggregative E. coli,Enteroinvasive E. coli,Enteroinvasive Escherichia coli
D006358 Hot Temperature Presence of warmth or heat or a temperature notably higher than an accustomed norm. Heat,Hot Temperatures,Temperature, Hot,Temperatures, Hot
D000903 Antibiotics, Antineoplastic Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms. Antineoplastic Antibiotics,Cytotoxic Antibiotics,Antibiotics, Cytotoxic
D013481 Superoxides Highly reactive compounds produced when oxygen is reduced by a single electron. In biological systems, they may be generated during the normal catalytic function of a number of enzymes and during the oxidation of hemoglobin to METHEMOGLOBIN. In living organisms, SUPEROXIDE DISMUTASE protects the cell from the deleterious effects of superoxides. Superoxide Radical,Superoxide,Superoxide Anion

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