Probing bacterial uptake of glycosylated ciprofloxacin conjugates.
Mono- and disaccharide-functionalised conjugates of the fluoroquinolone antibiotic ciprofloxacin have been synthesised and used as chemical probes of the bacterial uptake of glycosylated ciprofloxacin. Their antimicrobial activities against a panel of clinically relevant bacteria were determined: the ability of these conjugates to inhibit their target DNA gyrase and to be transported into the bacteria was assessed by using in vivo and in vitro assays. The data suggest a lack of active uptake through sugar transporters and that although the addition of monosaccharides is compatible with the inhibition of DNA gyrase, the addition of a disaccharide results in a significant decrease in antimicrobial activity.
Department of Chemistry, University of York, Heslington, York, YO10 5DD (UK).
Stephen J
SJ
Milner
Christopher T
CT
Carrick
Kevin G
KG
Kerr
Anna M
AM
Snelling
Gavin H
GH
Thomas
Anne-Kathrin
AK
Duhme-Klair
Anne
A
Routledge
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D002939:Ciprofloxacin / Q000737:chemistry*; D027081:DNA Gyrase / Q000737:chemistry / Q000378:metabolism; D004187:Disaccharides / Q000737:chemistry; D052978:Disk Diffusion Antimicrobial Tests; D006001:Glycoconjugates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006031:Glycosylation; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D009005:Monosaccharides / Q000737:chemistry
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004187:Disaccharides; D006001:Glycoconjugates; D009005:Monosaccharides; D002939:Ciprofloxacin; D027081:DNA Gyrase
antibiotics; bacteria; carbohydrates; ciprofloxacin; uptake