Preparation and antimicrobial assessment of 2-thioether-linked quinolonyl-carbapenems

J Antibiot (Tokyo). 1998 Sep;51(9):857-71. doi: 10.7164/antibiotics.51.857.

Abstract

This reports the synthesis and in vitro antimicrobial properties of a series of 2-thioether-linked quinolonyl-carbapenems. Although the title compounds exhibited broad spectrum activity, the MICs were generally higher than those observed for selected benchmark carbapenems, quinolonyl-penems, and quinolones. Enzyme assays suggested that the title compounds are potent inhibitors of penicillin binding proteins and inefficient inhibitors of bacterial DNA-gyrase. Uptake studies indicated that the new compounds are not substrates for the norA encoded quinolone efflux pump.

MeSH terms

  • Bacterial Proteins / drug effects
  • Carbapenems / chemical synthesis
  • Carbapenems / chemistry*
  • Carbapenems / pharmacology*
  • Carrier Proteins / drug effects
  • Cell Division
  • Gram-Negative Bacteria / drug effects*
  • Gram-Negative Bacteria / enzymology
  • Gram-Positive Bacteria / drug effects*
  • Gram-Positive Bacteria / enzymology
  • Hexosyltransferases / drug effects
  • Microbial Sensitivity Tests
  • Multidrug Resistance-Associated Proteins
  • Multienzyme Complexes / drug effects
  • Muramoylpentapeptide Carboxypeptidase / drug effects
  • Penicillin-Binding Proteins
  • Peptidyl Transferases / drug effects
  • Quinolones / chemistry*
  • Structure-Activity Relationship
  • Topoisomerase II Inhibitors

Substances

  • Bacterial Proteins
  • Carbapenems
  • Carrier Proteins
  • Multidrug Resistance-Associated Proteins
  • Multienzyme Complexes
  • PGE-5428060
  • Penicillin-Binding Proteins
  • Quinolones
  • Topoisomerase II Inhibitors
  • NorA protein, Staphylococcus
  • Peptidyl Transferases
  • Hexosyltransferases
  • Muramoylpentapeptide Carboxypeptidase