title: Osteoadsorptive bisphosphonate derivatives of fluoroquinolone antibacterials.
abstract: 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.
authors.affiliation: Research Group for Antibiotics, Hungarian Academy of Sciences, University of Debrecen, Hungary.
authors.forename: Pál
authors.initials: P
authors.lastname: Herczegh
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Buxton
authors.forename: James C
authors.initials: JC
authors.lastname: McPherson
authors.forename: Arpád
authors.initials: A
authors.lastname: Kovács-Kulyassa
authors.forename: Phyllis D
authors.initials: PD
authors.lastname: Brewer
authors.forename: Ferenc
authors.initials: F
authors.lastname: Sztaricskai
authors.forename: Gary G
authors.initials: GG
authors.lastname: Stroebel
authors.forename: Kent M
authors.initials: KM
authors.lastname: Plowman
authors.forename: Dan
authors.initials: D
authors.lastname: Farcasiu
authors.forename: John F
authors.initials: JF
authors.lastname: Hartmann
mesh_terms: 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
chemical_list: 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