Osteoadsorptive bisphosphonate derivatives of fluoroquinolone antibacterials.
Bisphosphonates conjugated to fluoroquinolone antibacterials through an intermediate carbon had better activity than conjugates lacking the carbon. Virtually all molar-based activity of these esterified bisphosphonate derivatives was identical to that of its parent. De-esterified free-acid forms retained good activity against most Gram-negative bacteria, but not against Gram-positives. A free-acid derivative remained bound to washed bone and completely inhibited Staphylococcus aureus growth. The more potent parent, ciprofloxacin, failed to bind significantly, and bacterial growth occurred.
Herczegh
Pál
P
Research Group for Antibiotics, Hungarian Academy of Sciences, University of Debrecen, Hungary.
Buxton
Thomas B
TB
McPherson
James C
JC
Kovács-Kulyassa
Arpád
A
Brewer
Phyllis D
PD
Sztaricskai
Ferenc
F
Stroebel
Gary G
GG
Plowman
Kent M
KM
Farcasiu
Dan
D
Hartmann
John F
JF
D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology; D002939:Ciprofloxacin / Q000737:chemistry*; D004164:Diphosphonates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015365:Enoxacin / Q000737:chemistry*; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000302:isolation & purification; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000302:isolation & purification; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D009643:Norfloxacin / Q000737:chemistry*; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015363:Quinolones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship; D013552:Swine
C455825:7-(4-(2,2-bisphosphonoethyl)piperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; D000890:Anti-Infective Agents; D004164:Diphosphonates; D010879:Piperazines; D015363:Quinolones; D015365:Enoxacin; D002939:Ciprofloxacin; D009643:Norfloxacin