Structure-activity relationship in the oxazolidinone-quinolone hybrid series: influence of the central spacer on the antibacterial activity and the mode of action.
Oxazolidinone-quinolone hybrids, which combine the pharmacophores of a quinolone and an oxazolidinone, were synthesised and shown to be active against a variety of susceptible and resistant Gram-positive and Gram-negative bacteria. The nature of the spacer greatly influences the antibacterial activity by directing the mode of action, that is quinolone- and/or oxazolidinone-like activity. The best compounds in this series have a balanced dual mode of action and overcome all types of resistance, including resistance to quinolones and linezolid, in clinically relevant Gram-positive pathogens.
Hubschwerlen
Christian
C
Morphochem AG, Schwarzwaldallee 215, CH 4058, Basel, Switzerland. christian.hubschwerlen@morphochem.ch
Specklin
Jean-Luc
JL
Baeschlin
Daniel K
DK
Borer
Yves
Y
Haefeli
Sascha
S
Sigwalt
Christine
C
Schroeder
Susanne
S
Locher
Hans H
HH
D000081:Acetamides / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D027101:DNA Topoisomerase IV / Q000037:antagonists & inhibitors; D024881:Drug Resistance, Bacterial; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D000069349:Linezolid; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D023303:Oxazolidinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015363:Quinolones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D015363:Quinolones; D027101:DNA Topoisomerase IV; D000069349:Linezolid