title: Preparation and antimicrobial assessment of 2-thioether-linked quinolonyl-carbapenems.
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.
authors.affiliation: Procter & Gamble Pharmaceuticals, Health Care Research Center, Mason, OH 45040-8006, USA.
authors.forename: P M
authors.initials: PM
authors.lastname: Hershberger
authors.forename: A G
authors.initials: AG
authors.lastname: Switzer
authors.forename: K E
authors.initials: KE
authors.lastname: Yelm
authors.forename: M C
authors.initials: MC
authors.lastname: Coleman
authors.forename: C A
authors.initials: CA
authors.lastname: Devries
authors.forename: F J
authors.initials: FJ
authors.lastname: Rourke
authors.forename: B W
authors.initials: BW
authors.lastname: Davis
authors.forename: W G
authors.initials: WG
authors.lastname: Kraft
authors.forename: T L
authors.initials: TL
authors.lastname: Twinem
authors.forename: P M
authors.initials: PM
authors.lastname: Koenigs
authors.forename: S M
authors.initials: SM
authors.lastname: Paule
authors.forename: R J
authors.initials: RJ
authors.lastname: Siehnel
authors.forename: P H
authors.initials: PH
authors.lastname: Zoutendam
authors.forename: R
authors.initials: R
authors.lastname: Imbus
authors.forename: T P
authors.initials: TP
authors.lastname: Demuth
mesh_terms: D001426:Bacterial Proteins / Q000187:drug effects; D015780:Carbapenems / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002352:Carrier Proteins / Q000187:drug effects; D002455:Cell Division; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000201:enzymology; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000201:enzymology; D006602:Hexosyltransferases / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009097:Multienzyme Complexes / Q000187:drug effects; D002267:Muramoylpentapeptide Carboxypeptidase / Q000187:drug effects; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases / Q000187:drug effects; D015363:Quinolones / Q000737:chemistry*; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors
chemical_list: D001426:Bacterial Proteins; D015780:Carbapenems; D002352:Carrier Proteins; D006602:Hexosyltransferases; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009097:Multienzyme Complexes; D002267:Muramoylpentapeptide Carboxypeptidase; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D015363:Quinolones; D059005:Topoisomerase II Inhibitors; C115625:PGE-5428060; C075040:NorA protein, Staphylococcus