title: Bisphosphonated fluoroquinolone esters as osteotropic prodrugs for the prevention of osteomyelitis.
abstract: 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.
authors.affiliation: Targanta Therapeutics Inc., 7170 Avenue Frederick Banting, Saint Laurent, Qué., Canada H4S 2A1.
authors.forename: Kelly S E
authors.initials: KS
authors.lastname: Tanaka
authors.forename: Tom J
authors.initials: TJ
authors.lastname: Houghton
authors.forename: Ting
authors.initials: T
authors.lastname: Kang
authors.forename: Evelyne
authors.initials: E
authors.lastname: Dietrich
authors.forename: Daniel
authors.initials: D
authors.lastname: Delorme
authors.forename: Sandra S
authors.initials: SS
authors.lastname: Ferreira
authors.forename: Laurence
authors.initials: L
authors.lastname: Caron
authors.forename: Frederic
authors.initials: F
authors.lastname: Viens
authors.forename: Francis F
authors.initials: FF
authors.lastname: Arhin
authors.forename: Ingrid
authors.initials: I
authors.lastname: Sarmiento
authors.forename: Dario
authors.initials: D
authors.lastname: Lehoux
authors.forename: Ibtihal
authors.initials: I
authors.lastname: Fadhil
authors.forename: Karine
authors.initials: K
authors.lastname: Laquerre
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Valérie
authors.initials: V
authors.lastname: Ostiguy
authors.forename: Hugo
authors.initials: H
authors.lastname: Poirier
authors.forename: Gregory
authors.initials: G
authors.lastname: Moeck
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Parr
authors.forename: Adel
authors.initials: A
authors.lastname: Rafai Far
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004952:Esters / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D024841:Fluoroquinolones / Q000737:chemistry*; D006801:Humans; D015394:Molecular Structure; D063065:Organophosphonates / Q000737:chemistry*; D010019:Osteomyelitis / Q000517:prevention & control*; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats
chemical_list: D004952:Esters; D024841:Fluoroquinolones; D063065:Organophosphonates; D011355:Prodrugs