1. Preparation and antimicrobial assessment of 2-thioether-linked quinolonyl-carbapenems
- Author
-
Zoutendam Ph, Switzer Ag, T. P. Demuth, Tracy L. Twinem, Imbus R, Paula M. Koenigs, Paule Sm, Coleman Mc, Kraft Wg, Hershberger Pm, F. J. Rourke, Davis Bw, Devries Ca, Yelm Ke, and Richard Siehnel
- Subjects
Penicillin binding proteins ,medicine.drug_class ,Microbial Sensitivity Tests ,Muramoylpentapeptide Carboxypeptidase ,Quinolones ,Gram-Positive Bacteria ,Chemical synthesis ,chemistry.chemical_compound ,Structure-Activity Relationship ,Thioether ,Bacterial Proteins ,Multienzyme Complexes ,Drug Discovery ,Gram-Negative Bacteria ,medicine ,Penicillin-Binding Proteins ,Topoisomerase II Inhibitors ,Antibacterial agent ,Pharmacology ,Biological activity ,Quinolone ,Antimicrobial ,Biochemistry ,chemistry ,Carbapenems ,Hexosyltransferases ,Peptidyl Transferases ,Efflux ,Multidrug Resistance-Associated Proteins ,Carrier Proteins ,Cell Division - 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.
- Published
- 1998