Bisphosphonated fluoroquinolone esters as osteotropic prodrugs for the prevention of osteomyelitis.
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.
Tanaka
Kelly S E
KS
Targanta Therapeutics Inc., 7170 Avenue Frederick Banting, Saint Laurent, Qué., Canada H4S 2A1.
Houghton
Tom J
TJ
Kang
Ting
T
Dietrich
Evelyne
E
Delorme
Daniel
D
Ferreira
Sandra S
SS
Caron
Laurence
L
Viens
Frederic
F
Arhin
Francis F
FF
Sarmiento
Ingrid
I
Lehoux
Dario
D
Fadhil
Ibtihal
I
Laquerre
Karine
K
Liu
Jing
J
Ostiguy
Valérie
V
Poirier
Hugo
H
Moeck
Gregory
G
Parr
Thomas R
TR
Rafai Far
Adel
A
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
D004952:Esters; D024841:Fluoroquinolones; D063065:Organophosphonates; D011355:Prodrugs