Osteoadsorptive bisphosphonate derivatives of fluoroquinolone antibacterials

被引:79
作者
Herczegh, P
Buxton, TB
McPherson, JC
Kovács-Kulyassa, A
Brewer, PD
Sztaricskai, F
Stroebel, GG
Plowman, KM
Farcasiu, D
Hartmann, JF
机构
[1] ElizaNor Biopharmaceut Inc, Princeton Jct, NJ 08550 USA
[2] Univ Debrecen, Hungarian Acad Sci, Res Grp Antibiot, Debrecen, Hungary
[3] Eisenhower Army Med Ctr, Dept Clin Invest, Ft Gordon, GA USA
[4] Augusta State Univ, Augusta, GA USA
关键词
D O I
10.1021/jm0105326
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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.
引用
收藏
页码:2338 / 2341
页数:4
相关论文
共 16 条
[1]  
BUXTON T, 2001, FASEB ABSTR
[2]   SYNTHESIS OF ETHENYLIDENEBIS(PHOSPHONIC ACID) AND ITS TETRAALKYL ESTERS [J].
DEGENHARDT, CR ;
BURDSALL, DC .
JOURNAL OF ORGANIC CHEMISTRY, 1986, 51 (18) :3488-3490
[3]  
DIEL IJ, 1998, NEW ENGL J MED, V339, P615
[4]  
FARCASIU D, 1999, Patent No. 5880111
[5]   Bisphosphonates: Preclinical aspects and use in osteoporosis [J].
Fleisch, HA .
ANNALS OF MEDICINE, 1997, 29 (01) :55-62
[6]   ORAL CIPROFLOXACIN COMPARED WITH PARENTERAL ANTIBIOTICS IN THE TREATMENT OF OSTEOMYELITIS [J].
GENTRY, LO ;
RODRIGUEZ, GG .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1990, 34 (01) :40-43
[7]   STRUCTURE-ACTIVITY-RELATIONSHIPS OF ANTI-BACTERIAL 6,7-DISUBSTITUTED AND 7,8-DISUBSTITUTED 1-ALKYL-1,4-DIHYDRO-4-OXOQUINOLINE-3-CARBOXYLIC ACIDS [J].
KOGA, H ;
ITOH, A ;
MURAYAMA, S ;
SUZUE, S ;
IRIKURA, T .
JOURNAL OF MEDICINAL CHEMISTRY, 1980, 23 (12) :1358-1363
[8]  
Lew D P, 1995, Drugs, V49 Suppl 2, P100
[9]   Bisphosphonates: A review of their pharmacokinetic properties [J].
Lin, JH .
BONE, 1996, 18 (02) :75-85
[10]  
MCKENNA CE, 1977, TETRAHEDRON LETT, P155