• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.40-47
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• 1997

New quinolones generally have a broad antibacterial spectrum against gram-positive, gram-negative, glucose-nonfermenting and anaerobic bacteria. Some of newly developed quinolones have potent activities against S. aureus including MRSA, S.pneumoniae including PRSP, B. fragilis, chlamydiae, mycoplasmas and mycobacteria as well, and show good activities against various strains resistant to antibacterial agents of other classes. Quinolones display postantibiotic effects in vitro and are bactericidal at concentrations similar to or twice that of the minimum inhibitory concentrations (MICs) for susceptible pathogens. In experimental murine infection models including systemic infections with various pathogens such as S. aureus, S. pyogenes, S. pneumoniae, E. coli and P. aeruginosa, quinolones have shown good oral efficacy as well as parenteral efficacy. Good oral absorption and good tissue penetration of quinolones account for good therapeutic effects in clinical settings. The target of quinolones are two structurally related type II topoisomerases, DNA gyrase and DNA topoisomerase IV. Quinolones are shown to stabilize the ternary quinolone-gyrase-DNA complex and inhibit the religation of the cleaved double-stranded DNA. Bacteria can acquire resistance to quinolones by mutations of these target enzymes. Mutation sites and amino acid changes in DNA gyrase and DNA topoisomerase IV are similar in the organisms examined, suggesting that the mechanism of quinolone resistance in the target enzymes is essentially the same among various organisms. Quinolones act on both the target enzymes to different degrees depending on the organisms or agents tested, and bacteria become highly resistant to quinolones in a step-wise fashion. Incomplete cross-resistance among quinolones in some strains of E. coli and S. aureus suggests the possibility of finding quinolones active against quinolone-resistant strains which are prevailing now. To find such quinolones, the potency toward two target enzymes and the membrane permeability including influx and/or efflux systems should be taken into account.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.33-39
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• 1997

• YAKHAK HOEJI
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• v.38 no.6
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• pp.664-672
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• 1994

Eighteen new hybrid bivalent ligand quinolones that contain two different type of pharmacophores in a single molecule were prepared and evaluated for in viかo antibacterial activity. Hybrid bivalent ligands p-nitrobenzyloxycarbonyl quinolones were prepared by the treatment of active esters of succinyl fluoroquinolones with 1,7-disubstituted fluoroquinolone carboxylic acids in DMF. Eighteen final quinolone carboxylic acids were obtained by the reduction of compounds $25{\sim}42$ with hydrogen in the presence of 10% Pd-C. Among these derivatives, compound[56] showed the most potent antibacterial activity against a wide range of microoranisms.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.48-56
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• 1997

• Bulletin of the Korean Chemical Society
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• v.13 no.5
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• pp.571-573
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• 1992

• YAKHAK HOEJI
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• v.55 no.1
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• pp.22-31
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• 2011

This systematic review was conducted to assess the clinical effect of ocular fluoroquinolones used for the treatment of bacterial conjunctivitis. A literature search for randomized controlled clinical trials registered up to January 2010 based on PubMed database, using the following search terms: conjunctivitis and fluoroquinolones (besifloxacin, moxifloxacin, gatifloxacin, levofloxacin, lomefloxacin, ciprofloxacin and ofloxacin) were performed. Pooled data on the clinical resolution and bacterial eradication rates derived from selected 16 studies were reported as the relative risk (RR) and 95% confidence interval (95% CI) compared with placebo. Early clinical resolution and microbiological eradication rates in placebo were 28% and 62% respectively. Fluoroquinolones were significantly effective comparing to placebo: early RR 1.94 (95% CI 1.60~2.34) and late RR 1.30 (1.19~1.43) in clinical resolution rates, and early RR 1.75 (1.58~1.94) and late RR 1.28 (1.18~1.39) in microbiological eradication rates. Besifloxacin, ciprofloaxain and moxifloxacin in clinical resolution, and besifloxacin and levofloxacin in microbiological eradication showed higher RRs than pooled overall fluoroquinolones' RRs. New quinolones had higher antibacterial potencies for all pathogens isolated from bacterial conjunctivitis and resistant isolates than old generation quinolones. In conclusion, ocular 7 fluoroquinolones were all effective than placebo for bacterial conjunctivitis and there were differences between quinolones in early and late clinical resolutions and microbiological eradications, and no differences in safety comparing to placebo.

• YAKHAK HOEJI
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• v.48 no.3
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• pp.202-206
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• 2004

New asymmetric dimers, N,N'-dialkyl-4'-hydroxy-4-oxo-2,2',3,3'-tetrahydro-2,2'-diphenyl-4,4'-quinolones 3a-f were synthesized through the dehydration and dea1coholation of N-alkylanilines and ethyl benzoylacetate. Dimers 3a-f were identified by NMR, IR and GC-MS. A series of dimer 3a-f has been synthesized using acid-catalyzed one-pot reaction that involved the condensation, cyc1ization and dimerization. Similarly, the 6,6'-methoxy (or 7,7'-methoxy) substituted dimers were prepared from N-alkyl-meta-(or para)-anisidines. Formation of dimers was undertaken with p-toluenesulfonic acid (p-TSA) at 90∼11$0^{\circ}C$ in toluene for 2∼6 hours over the Dean-Stark apparatus.

• Journal of fish pathology
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• v.9 no.2
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• pp.185-193
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• 1996

Extensive acquirement of drug resistance to traditional antibacterial agents poses a serious problem to eel aquaculturists. To collect the basic information for new drug development in the future, we assessed the in vitro antibacterial efficacy of 14 new quinolones with 75 isolates of Edwardsiella tarda from local aquaculture tanks of Anguilla japonica. Of all tested quinolones under development or marketed for human use, DU-6859 was most potent with its $MIC_{50}$ value of $0.05{\mu}g$/ml in broth microdilution assay. The drugs whose $MIC_{50}$ values ranged from 0.2 to $0.78{\mu}g$/ml were T-3762, Bay-y3118, ciprofloxacin, norfloxacin, ofloxcin and tosufloxacin. The weakest group of drugs, with their $MIC_{50}$ being 1.56-$3.13{\mu}g$/ml, were difloxacin, sparfloxacin, fleroxacin, Q-35, amifloxacin, lomefloxacin and enoxacin. The number of resistant strains, when arbitrarily defined with their MICs of $\geq6.25{\mu}g$/ml, was : 3 to T-3762, 3 to Bay-y3118, 44 to difloxacin, 16 to sparfloxacin, 13 to ciprofloxacin, 19 to fleroxacin, 36 to Q-35). 31 to amifloxacin, 5 to norfloxacin, 13 to ofloxacin, 31 to lomefloxacin, 41 to enoxacin, 12 to tosufloxacin and 0% to DU-6859, respectively. This information can be taken into consideration for the future development of fisheries antibacterial quinolones.

• Bulletin of the Korean Chemical Society
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• v.25 no.8
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• pp.1269-1272
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• 2004

• YAKHAK HOEJI
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• v.41 no.3
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• pp.312-320
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• 1997

Pharmacokinetics and tissue distribution of DWP20349 and 20351, new quinolones, were examined in rats after a single intravenous and oral administration. Analyses of DWP20349 an d DWP20351 in plasma, tissue, and urine were determined by both HPLC and bioassay(microbiological assay). The plasma concentrations of the drugs declined biexponentially. The terminal half-lives ($t_{1/2\beta}$) of drugs were about 114 min (DWP20349) and 105 min (DWP20351) after intravenous dosing, and were 77 min (DWP20349) and 79 min (DWP20351) after oral dosing. The volume of distrbution at steady-state ($Vd_{ss}$) and total body clearances ($Cl_t$) of DWP20349 and DWP20351 were 760 ml/kg and 1126 ml/kg, and 5ml/min/kg and 10 ml/min/kg, respectively. The extents of bioavailability if DWP20349 and DWP20351 after oral administration were 29% and 28%, respectively. 24 h urinary recoveries measured by bioassay were 1.8% (DWP20349) and 1.3% (DWP20351) after oral dosing, and 2.4% (DWP20349) and 1.9% (DWP20351) after intravenous dosing. Plasma protein binding ratios ranged from 87%-90% (DWP20349) and 61%-68% (DWP20351). These drugs were highly distrbuted by the order of lung, kidney, liver and plasma (DWP20394), and lung, liver, kidney and plasma (DWP20351) after 1 hour orally administered.