Quinolones

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Targets

Type II Topoisomerases

  • DNA Gyrase
  • Topoisomerase IV[1]
    • inhibition by norfloxacin reduces activity to a rate of 1/100 the normal level[2]


Results in replication fork collapse and induction of the SOS response due to permanent double-stranded breaks caused by the formation of poisonous protein:DNA adducts.

Resistant Alleles

  • ParC

Usage Examples and Notes

  • Norfloxacin[3]
  • Oxolinic acid and nalidixic acid interact with the same target to inhibit replication DNA synthesis. Although nalidixic acid is used extensively, oxolinic acid has ben found to be 10-fold more active of an inhibitor. Mutants with resistance to one drug also show resistance to the other drug. [4]

References

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  1. Khodursky, AB et al. (1995) Topoisomerase IV is a target of quinolones in Escherichia coli. Proc. Natl. Acad. Sci. U.S.A. 92 11801-5 PubMed
  2. Zechiedrich, EL & Cozzarelli, NR (1995) Roles of topoisomerase IV and DNA gyrase in DNA unlinking during replication in Escherichia coli. Genes Dev. 9 2859-69 PubMed
  3. Lopez, CR et al. (2005) A role for topoisomerase III in a recombination pathway alternative to RuvABC. Mol. Microbiol. 58 80-101 PubMed
  4. Staudenbauer, WL (1976) Replication of Escherichia coli DNA in vitro: inhibition by oxolinic acid. Eur. J. Biochem. 62 491-7 PubMed