Preparation and antimicrobial assessment of 2-thioether-linked quinolonyl-carbapenems.
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.
Hershberger
P M
PM
Procter & Gamble Pharmaceuticals, Health Care Research Center, Mason, OH 45040-8006, USA.
Switzer
A G
AG
Yelm
K E
KE
Coleman
M C
MC
Devries
C A
CA
Rourke
F J
FJ
Davis
B W
BW
Kraft
W G
WG
Twinem
T L
TL
Koenigs
P M
PM
Paule
S M
SM
Siehnel
R J
RJ
Zoutendam
P H
PH
Imbus
R
R
Demuth
T P
TP
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
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