Aminocoumarins

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Novobiocin, an aminocoumarin

The aminocoumarins are antibiotics that inhibit the cell division of bacteria by inhibiting gyrase and are classed as gyrase inhibitors . They were first obtained from bacteria of the genus Streptomyces , the best-known representative of which Streptomyces coelicolor is the first fully sequenced Streptomyces species.

The aminocoumarins include antibiotics

  • Novobiocin , which is approved under the name Albamycin in the USA, where it was first prepared from a species of actinomycete in 1955
  • Coumermycin
  • Clorobiocin

The latter two are not used clinically because the toxicity of the respective substance is too high and the water solubility is too low.

A common structural feature of aminocoumarin antibiotics is a 3-amino-4,7-dihydroxycoumarin ring, which is linked to a sugar in the 7-position and, for example, a benzoic acid derivative in the 3-position. In contrast to the fluoroquinolones (also gyrase inhibitors), aminocoumarins bind to the gyrB subunit. They inhibit the binding of adenosine triphosphate to the B subunit of gyrase. Various mutations have been described that confer antibiotic resistance to aminocoumarins.

Individual evidence

  1. ↑ SD Bentley, KF Chater, AM Cerdeño-Tárraga, GL Challis, NR Thomson, KD James, DE Harris, MA Quail, H. Kieser, D. Harper, A. Bateman, S. Brown, G. Chandra, CW Chen, M. Collins, A. Cronin, A. Fraser, A. Goble, J. Hidalgo, T. Hornsby, S. Howarth, CH Huang, T. Kieser, L. Larke, L. Murphy, K. Oliver, S. O 'Neil, E. Rabbinowitsch, MA Rajandream, K. Rutherford, S. Rutter, K. Seeger, D. Saunders, S. Sharp, R. Squares, S. Squares, K. Taylor, T. Warren, A. Wietzorrek, J. Woodward, BG Barrell, J. Parkhill, DA Hopwood: Complete genome sequence of the model actinomycete Streptomyces coelicolor A3 (2). In: Nature. Volume 417, Number 6885, May 2002, pp. 141-147, doi : 10.1038 / 417141a , PMID 12000953 .
  2. ↑ Karl Wurm, AM Walter: Infectious Diseases. In: Ludwig Heilmeyer (ed.): Textbook of internal medicine. Springer-Verlag, Berlin / Göttingen / Heidelberg 1955; 2nd edition, ibid. 1961, pp. 9–223, here: p. 53.
  3. ↑ FT Tsai, OM Singh, T. Skarzynski, AJ Wonacott, S. Weston, A. Tucker, RA Pauptit, AL Breeze, JP Poyser, R. O'Brien, JE Ladbury, DB Wigley: The high-resolution crystal structure of a 24-kDa gyrase B fragment from E. coli complexed with one of the most potent coumarin inhibitors, clorobiocin. In: Proteins. Volume 28, Number 1, May 1997, pp. 41-52, PMID 9144789 .
  4. ↑ U. Galm, S. Heller, S. Shapiro, M. Page, SM Li, L. Heide: Antimicrobial and DNA gyrase-inhibitory activities of novel clorobiocin derivatives produced by mutasynthesis. In: Antimicrobial agents and chemotherapy. Volume 48, Number 4, April 2004, pp. 1307-1312, PMID 15047534 , PMC 375324 (free full text).
  5. ^ A. Maxwell: The interaction between coumarin drugs and DNA gyrase. In: Molecular microbiology. Volume 9, Number 4, August 1993, pp. 681-686, PMID 8231802 .
  6. ↑ a b A. Maxwell, DM Lawson: The ATP-binding site of type II topoisomerases as a target for antibacterial drugs. In: Current topics in medicinal chemistry. Volume 3, Number 3, 2003, pp. 283-303, PMID 12570764 .
  7. ↑ M. Fujimoto-Nakamura, H. Ito, Y. Oyamada, T. Nishino, J.-I. Yamagishi: Accumulation of Mutations in both gyrB and parE Genes Is Associated with High-Level Resistance to Novobiocin in Staphylococcus aureus . In: Antimicrob. Agents Chemother. . 49, No. 9, 2005, pp. 3810-3815. doi : 10.1128 / aac.49.9.3810-3815.2005 .
  8. ^ E. Schmutz, A. Mühlenweg, SM Li, L. Heide: Resistance genes of aminocoumarin producers: two type II topoisomerase genes confer resistance against coumermycin A1 and clorobiocin. In: Antimicrobial agents and chemotherapy. Volume 47, Number 3, March 2003, pp. 869-877, PMID 12604514 , PMC 149333 (free full text).