Osteoadsorptive bisphosphonate derivatives of fluoroquinolone antibacterials

Pál Herczegh; Thomas B. Buxton; James C. McPherson; Árpád Kovács-Kulyassa; Phyllis D. Brewer; Ferenc Sztaricskai; Gary G. Stroebel; Kent M. Plowman; Dan Farcasiu; John F. Hartmann

doi:10.1021/jm0105326

Osteoadsorptive bisphosphonate derivatives of fluoroquinolone antibacterials

Pál Herczegh, Thomas B. Buxton, James C. McPherson, Árpád Kovács-Kulyassa, Phyllis D. Brewer, Ferenc Sztaricskai, Gary G. Stroebel, Kent M. Plowman, Dan Farcasiu, John F. Hartmann

Research output: Contribution to journal › Article › peer-review

80 Scopus citations

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.

Original language	English (US)
Pages (from-to)	2338-2341
Number of pages	4
Journal	Journal of Medicinal Chemistry
Volume	45
Issue number	11
DOIs	https://doi.org/10.1021/jm0105326
State	Published - May 23 2002
Externally published	Yes

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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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.",

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doi = "10.1021/jm0105326",

language = "English (US)",

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T1 - Osteoadsorptive bisphosphonate derivatives of fluoroquinolone antibacterials

AU - Herczegh, Pál

AU - Buxton, Thomas B.

AU - McPherson, James C.

AU - Kovács-Kulyassa, Árpád

AU - Brewer, Phyllis D.

AU - Sztaricskai, Ferenc

AU - Stroebel, Gary G.

AU - Plowman, Kent M.

AU - Farcasiu, Dan

AU - Hartmann, John F.

PY - 2002/5/23

Y1 - 2002/5/23

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AB - 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.

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Osteoadsorptive bisphosphonate derivatives of fluoroquinolone antibacterials

Abstract

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