Ly lower protein binding. Cleavable complexes with bacterial and human topoisomerases. Fluoroquinolones interact with DNA gyrase and topoisomerase IV, DNA gyrase in maintaining DNA supercoiling SGX-523 corresponding one of the DNA synthesis and transcription, w While the topoisomerase IV chromosomal in DNA decatenation and chromosome segregation involved is involved. In addition to inhibition of the catalytic activity of t of the enzymes, quinolones form a stable DNA-enzyme quinolone cleavable complex. The complex formation inhibits the enzymatic DNA quinolones him DNA synthesis is reversible and first causes bacteriostatic growth inhibition. Irreversible, t Harmful micro-and doppelstr Be Independent breaks when the complex dissociates released.
The interaction of fluoroquinolones with the enzyme DNA complex adversely chtigt The replication of chromosomes and chromosome segregation. ABT 492 is a potent inhibitor of both topoisomerases E. coli and S. aureus, WZ3146 as measured by the cleavable complex formation. Topoisomerase IV is generally sensitive to interactions quinolones as DNA gyrase in Gram-positive species. Trovafloxacin and ciprofloxacin showed 8 and 19 times more energy, and S. aureus aureus topoisomerase IV than against DNA gyrase of S.. The interaction of ABT 492 with two S. aureus topoisomerases was similar, with three grams Activity eren t against DNA gyrase than against topoisomerase IV A direct comparison was almost three times more active than ABT 492 and trovafloxacin was approximately six times aureus active than ciprofloxacin against DNA gyrase of S.
. Although fluoroquinolones interact with both enzymes, k Nnten DNA gyrase a goal to be faster than Table 2. Comparison of MIC and MBC Resistancea species or strain MIC MBC MIC MBC MIC MBC ABT 492 ciprofloxacin-sensitive S. pneumoniae 2486 0002 .002 4 8 Pen R 6502 0.002 0.002 4 8 MEF and Pen I 5649 0.004 0.004 0.002 0.002 16 32 8 August 5979 ermB quinolones R 7240 128 128 0.03 0.06 S. aureus sensitive 1662 0,002 0.002 0.06 0.06 0.03 0.03 1967 E. faecalis sensitive E. coli 0.5 0.5 1298 0008 0.03 0.004 sensitive H. influenzae Sensitive 0.008 1435 0,002 0.002 0.008 0.015 0.002 0.002 0.008 0.015 M. catarrhalis 2604, a pin, penicillin, R resistant, I intermediate. TABLE 3 Plasma protein binding to plasma proteins% antibiotic Rat serum bound to human serum ABT 492 89.
0 77.0 96.5 68.7 27.9 32.6 3266 ciprofloxacin trovafloxacin Nilius et al. Antimicrob. Agents Chemother. Topoisomerase IV due to the interaction between fluoroquinolones and DNA gyrase, which move away from the replication fork positive supercoils, inhibits DNA replication faster than the interaction with topoisomerase IV, which is located behind it. Thus showing the interaction with DNA gyrase st More strongly with the enzyme from S. aureus is probably responsible for the gr Te antibacterial activity t of ABT 492 against Gram-positive organisms compared with those of ciprofloxacin and trovafloxacin. For Gram-negative species, DNA gyrase is usually more sensitive than topoisomerase IV on the interaction of fluoroquinolones. In this study, ciprofloxacin and trovafloxacin almost 10 times st Stronger than with DNA gyrase, topoisomerase IV interacted with. However, the interactions of ABT 492 with two topoisomerases E. coli were approximately equal. All three quinolones were highly active against DNA gyrase from E. coli and demonstrated ha