Bisphosphonated fluoroquinolone esters as osteotropic prodrugs for the prevention of osteomyelitis

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• 作者：Kelly S.E. Tanaka ; Tom J. Houghton ; Ting Kang ; Evelyne Dietrich ; Daniel Delorme ; S ; ra S. Ferreira ; Laurence Caron ; Frederic Viens ; Francis F. Arhin ; Ingrid Sarmiento ; Dario Lehoux ; Ibtihal Fadhil ; Kar
• 关键词：Osteomyelitis ; Fluoroquinolone ; Bisphosphonates ; Drug delivery ; Prodrug
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2008
• 出版时间：15 October 2008
• 年：2008
• 卷：16
• 期：20
• 页码：9217-9229
• 全文大小：319 K

文摘

Osteomyelitis is a difficult to treat bacterial infection of the bone. Delivering antibacterial agents to the bone may overcome the difficulties in treating this illness by effectively concentrating the antibiotic at the site of infection and by limiting the toxicity that may result from systemic exposure to the large doses conventionally used. Using bisphosphonates as osteophilic functional groups, different forms of fluoroquinolone esters were synthesized and evaluated for their ability to bind bone and to release the parent antibacterial agent. Bisphosphonated glycolamide fluoroquinolone esters were found to present a profile consistent with effective and rapid bone binding and efficient release of the active drug moiety. They were assessed for their ability to prevent bone infection in vivo and were found to be effective when the free fluoroquinolones were not.