Antofloxacin free base is prepared from antofloxacin hydrochloride by removing hydrogen chloride. Its crystal is obtained by slow evaporation of an acetonitrile-methanol mixed solution. Single-crystal X-ray diffractio...Antofloxacin free base is prepared from antofloxacin hydrochloride by removing hydrogen chloride. Its crystal is obtained by slow evaporation of an acetonitrile-methanol mixed solution. Single-crystal X-ray diffraction reveals that the crystallography belongs to a triclinic PI space group with cell parameters： a = 0. 663 07（13） nm, b = 0. 898 39（18） nm, c = 1. 569 0（3） nm, α = 75.12（3）°,β = 87.92（3）°, γ = 77.57 （3）°. Antofloxacin shows no fluorescence in solution, but the crystalline state emits strong green light at 510 nm under the excitation of 360 nm, indicating a fluorescence enhancement induced by aggregation. It demonstrates that intermolecular packing and interaction in the crystal lead to the improved fluorescence quantum yield. These results provide important intbrmation for the further exploration of the structure-activity relationship of antofloxacin and the development of new drugs.展开更多
Objectives: To determine the susceptibilities of M.hominis and U. urealyticum to fluoroquinolones forthe instruction of reasonable clinical application ofantibiotics.Method: The susceptibilities of M. hominis and U.ur...Objectives: To determine the susceptibilities of M.hominis and U. urealyticum to fluoroquinolones forthe instruction of reasonable clinical application ofantibiotics.Method: The susceptibilities of M. hominis and U.urealyticum to six fluoroquinolones were determinedby the broth dilution method.Results: Sparfloxacin and gatifloxacin were veryactive with MIC50S of 0.03125 and 0.25 μg/ml againstM. hominis, 0.25 and 0.5 μg/ml against U. urealyticum,respectively. Levofloxacin and ofloxacin had MIC50S of1 μg/ml and 2 μg/ml, respectively against both species.Norfloxacin was less effective against both species at16 and 32 μg/ml. Ciprofloxacin was unusual in thatthe MIC50S varied fourfold between species, with 2 μg/ml against M. hominis and 8 μg/ml against U.urealyticum.Conclusions: The results can provide useful infor-mation for selecting fluoroquinolones for treatmentof urogenital mycoplasma infections.展开更多
\ 2Alkyl6oxo8fluoro9(4methylpiperazin1yl)6Himidazo(4,5,1ij)quinoline5carboxylic acids (2Ab～2Ae) were prepared by condensation of ethyl 6fluoro7(4methylpiperazin1yl)8amino1,4dihydro4oxo3quinolinecarboxylate (5A) wit...\ 2Alkyl6oxo8fluoro9(4methylpiperazin1yl)6Himidazo(4,5,1ij)quinoline5carboxylic acids (2Ab～2Ae) were prepared by condensation of ethyl 6fluoro7(4methylpiperazin1yl)8amino1,4dihydro4oxo3quinolinecarboxylate (5A) with the aliphatic acids in PPA. Other target compounds 2Af～2Ah, 2Bc, 2Cc, 2Aa～2Da, 2Bi and 2Ci were prepared by the condensation of 6fluoro7nitrogencontaining heterocycle8amino1,4dihydro4oxo3quinolinecarboxylic acids (9A～9D) with the corresponding acids in PPA or with ethyl orthoformate or by the diazotisation of 9B and 9C, respectively. Only 2Ab and 2Ac showed moderate antibacterial activity in in vitro test.展开更多
AIM： To study the relationship between quantitative structure and pharmacokinetics （QSPkR） of fluorocluinolone antibacterials.METHODS： The pharmacokinetic （PK） parameters of oral fluoroquinolones were collected ...AIM： To study the relationship between quantitative structure and pharmacokinetics （QSPkR） of fluorocluinolone antibacterials.METHODS： The pharmacokinetic （PK） parameters of oral fluoroquinolones were collected from the literature. These pharmacokinetic data were averaged, 19 compounds were used as the training set, and 3 served as the test set. Genetic function approximation （GFA） module of Cerius2 software was used in QSPkR analysis.RESULTS： A small volume and large polarizability and surface area of substituents at C-7 contribute to a large area under the curve （AUC） for fluoroquinolones. Large polarizability and small volume of substituents at N-1 contribute to a long half life elimination.CONCLUSION： QSPkR models can contribute to some fluoroquinolones antibacterials with excellent pharmacokinetic properties.展开更多
For preparing fluorinated quinolone antibiotic medicine locally used in stomatology, simultaneous determination of norfloxacin, ciprofloxacin, and enoxacin was carried out by multiphase ion chromatography with fluores...For preparing fluorinated quinolone antibiotic medicine locally used in stomatology, simultaneous determination of norfloxacin, ciprofloxacin, and enoxacin was carried out by multiphase ion chromatography with fluorescence detection. Quinolone antibiotics were separated by Dionex OmniPac PAX-500 column with an eluent of 15 mmol/L H2SO4 and 35% methanol （v/v） at a flow-rate of 1.0 ml/min and detected with fluorescence with excitation and emission wave lengths of 347 ran and 420 ran respectively. The detection limits （S/N=3） of norfloxacin, ciprofloxacin and enoxacin were 50, 105 and 80 ng/ml respectively. The relative standard deviations of retention time, peak area and peak height were less than 1.1% and good linear relationship resulted. The developed method was applied to pharmaceutical formulations and biological fluids.展开更多
AIM:To compare triple therapy vs quadruple therapy for 10 d as first-line treatment ofHelicobacter pylori(H.pylori) infection.METHODS:Consecutive H.pylori positive patients never treated in the past for this infection...AIM:To compare triple therapy vs quadruple therapy for 10 d as first-line treatment ofHelicobacter pylori(H.pylori) infection.METHODS:Consecutive H.pylori positive patients never treated in the past for this infection were randomly treated with triple therapy of pantoprazole(PAN) 20 mg bid,amoxicillin(AMO) 1 g bid and moxifloxacin(MOX) 400 mg bid for 10 d(PAM) or with quadruple therapy of PAN 20 mg bid,AMO 1 g bid,MOX 400 mg bid and bismuth subcitrate 240 mg bid for 10 d(PAMB).All patients were found positive at 13 C-Urea breath test(UBT) performed within ten days prior to the start of the study.A successful outcome was confirmed with an UBT performed 8 wk after the end of treatment.χ 2 analysis was used for statistical comparison.Per protocol(PP) and intention-to-treat(ITT) values were also calculated.RESULTS:Fifty-seven patients were enrolled in the PAM group and 50 in the PAMB group.One patient in each group did not return for further assessment.Eradication was higher in the PAMB group(negative:46 and positive:3) vs the PAM group(negative:44 and positive:12).The H.pylori eradication rate was statistically significantly higher in the PAMB group vs the PAM group,both with the PP and ITT analyses(PP:PAMB 93.8%,PAM 78.5%,P < 0.02;ITT:PAMB 92%,PAM 77.1 %,P <0.03).CONCLUSION:The addition of bismuth subcitrate can be considered a valuable adjuvant to triple therapy in those areas where H.pylori shows a high resistance to fluoroquinolones.展开更多
According to a review article by Biecker et al published in a previous issue of World Journal of Gastroenterology in March 2011,intestinal decontamination with norfloxacin remains the mainstay of primary prophylaxis o...According to a review article by Biecker et al published in a previous issue of World Journal of Gastroenterology in March 2011,intestinal decontamination with norfloxacin remains the mainstay of primary prophylaxis of spontaneous bacterial peritonitis(SBP) at the expense of development of quinolone-resistant bacteria after long-term use.In our research,the administration of a 4-wk regimen with rifaximin 1200 mg/d reduced significantly the ascitic neutrophil count in cirrhotic patients with sterile ascites in line with a significant decrease in plasma endotoxin levels.Our observations concur with recent findings,showing a significantly reduced 5-year probability of SBP in cirrhotic patients taking rifaximin.展开更多
OBJECTIVE: To study the resistance mechanism of clinical isolates of Ureaplasma urealyticum resistant to fluoroquinolones. METHODS: Thirteen isolates of Ureaplasma urealyticum resistant to six fluoroquinolones were se...OBJECTIVE: To study the resistance mechanism of clinical isolates of Ureaplasma urealyticum resistant to fluoroquinolones. METHODS: Thirteen isolates of Ureaplasma urealyticum resistant to six fluoroquinolones were selected out of 184 clinical isolates and their QRDRs (quinolone resistance-determining region) gyrA, gyrB, parC and parE were amplified by PCR. Sequencing results were compared to those susceptible reference strains and a comparison of deduced amino acid sequences were performed. RESULTS: Sequence comparison revealed a C to A change at 87nt of gyrA QRDR leading to the substitution of Asp95 with glutamic acid and a C to T change at 50nt of parC QRDR leading to the substitution of Ser80 with leucine. CONCLUSION: These results suggest that a C to A change at 87nt of gyrA QRDR and a C to T change at 50nt of parC QRDR are associated with fluoroquinolone resistance of Ureaplasma urealyticum.展开更多
Objective To evaluate the role of outer membrane protein (Omp) F-deficiency and active efflux in the accumulation of hydrophilic fluoroquinolones ciprofloxacin (CPLX) and lomefloxacin (LMLX) in resistant E. coli ...Objective To evaluate the role of outer membrane protein (Omp) F-deficiency and active efflux in the accumulation of hydrophilic fluoroquinolones ciprofloxacin (CPLX) and lomefloxacin (LMLX) in resistant E. coli strains. Methods Fluoroquinolone accumulation in bacteria and the effect of active efflux were measured by a fluorescence method. The outer membrane proteins of the bacteria were analysed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). E. coli strains in this study included control strains JF701 and JF703 that are OmpC- or OmpF-deficient mutants of E. coli K-12, respectively, and the fluoroquinolone susceptible strain the fluoroquinolone susceptible strain of Escherichia coli (Ecs) and its in vitroselected resistant strains R2 and R256, and the clinical resistant isolates R5 and R6. Results The steady-state accumulation concentration of each drug in Ecs appeared to be the same as in JF701, while in the OmpF- deficient strain JF703, it was 1/5 CPLX or 1/2 LMLX lower than that in JF701, but JF703 was still susceptible to fluoroquinolones. On the other hand, compared with susceptible strains, a 2- to 10-fold decrease in the accumulation of each drug was found in the resistant strains except R2, in which the accumulation was slightly higher than in JF703. After the addition of 2,4-dinitrophenol (DNP), accumulation of each drug increased, especially in resistant strains, indicating that the function of the active efflux (pump) system in these bacteria had been enhanced dramatically. Furthermore, both OmpF and OmpC in Ecs, OmpF-deficiency in R2 and R256 and OmpC-deficiency in R5 and R6 were observed.Conclusion The decreased accumulation of hydrophilic fluoroquinolones in E. coli involved OmpF-deficiency and active efflux (pump), and the latter may be an important factor.展开更多
To study the resistance mechanism of clinical isolates of Ureaplasma urealyticum resistant to fluoroquinolones Methods Thirteen isolates of Ureaplasma urealyticum resistant to six fluoroquinolones were selected out ...To study the resistance mechanism of clinical isolates of Ureaplasma urealyticum resistant to fluoroquinolones Methods Thirteen isolates of Ureaplasma urealyticum resistant to six fluoroquinolones were selected out of 184 clinical isolates and their QRDRs (quinolone resistance determining region) gyrA, gyrB, parC and parE were amplified by PCR Sequencing results were compared to those susceptible reference strains and a comparison of deduced amino acid sequences were performed Results Sequence comparison revealed a C to A change at 87nt of gyrA QRDR leading to the substitution of Asp95 with glutamic acid and a C to T change at 50nt of parC QRDR leading to the substitution of Ser80 with leucine Conclusion These results suggest that a C to A change at 87nt of gyrA QRDR and a C to T change at 50nt of parC QRDR are associated with fluoroquinolone resistance of Ureaplasma urealyticum展开更多
The reactions between gatifloxacin(GFX) and various one-electron oxidants,such as ˙OH,N3˙,Br2˙ˉ,and SO4˙ˉ,have been studied by pulse radiolysis techniques.The GFX radical anion formed in the reaction of GFX with...The reactions between gatifloxacin(GFX) and various one-electron oxidants,such as ˙OH,N3˙,Br2˙ˉ,and SO4˙ˉ,have been studied by pulse radiolysis techniques.The GFX radical anion formed in the reaction of GFX with eaqˉ could either be protonated or deprotonated,and the absorption of GFX radical anion was located at 390 nm.The transient species produced by the reaction of GFX with ˙OH radical shows a broad band in the 380?600 nm region with a shoulder,while the oxidation by N3˙,SO4˙ˉ,and Br2˙ˉ results in an absorption band with λmax = 370 nm.At neutral condition(pH 7),the rate constants of GFX reacting with ˙OH,N3˙,Br2˙ˉ,SO4˙ˉ and eaqˉ are estimated to be 1.0 × 1010,3.1 × 109,2.8 × 109,3.0 × 109,and 1.8 × 1010 dm3 mol?1 s?1,respectively.From the pH dependence on the formation of electron adducts and on the rate constant of GFX with eaqˉ,the pKa of GFX radical anion is estimated to be 5.5 and 9.3.展开更多
文摘Antofloxacin free base is prepared from antofloxacin hydrochloride by removing hydrogen chloride. Its crystal is obtained by slow evaporation of an acetonitrile-methanol mixed solution. Single-crystal X-ray diffraction reveals that the crystallography belongs to a triclinic PI space group with cell parameters： a = 0. 663 07（13） nm, b = 0. 898 39（18） nm, c = 1. 569 0（3） nm, α = 75.12（3）°,β = 87.92（3）°, γ = 77.57 （3）°. Antofloxacin shows no fluorescence in solution, but the crystalline state emits strong green light at 510 nm under the excitation of 360 nm, indicating a fluorescence enhancement induced by aggregation. It demonstrates that intermolecular packing and interaction in the crystal lead to the improved fluorescence quantum yield. These results provide important intbrmation for the further exploration of the structure-activity relationship of antofloxacin and the development of new drugs.
基金Financially supported by a grant from the Education Com-mittee of Hunan Province (No.ooAoo9)
文摘Objectives: To determine the susceptibilities of M.hominis and U. urealyticum to fluoroquinolones forthe instruction of reasonable clinical application ofantibiotics.Method: The susceptibilities of M. hominis and U.urealyticum to six fluoroquinolones were determinedby the broth dilution method.Results: Sparfloxacin and gatifloxacin were veryactive with MIC50S of 0.03125 and 0.25 μg/ml againstM. hominis, 0.25 and 0.5 μg/ml against U. urealyticum,respectively. Levofloxacin and ofloxacin had MIC50S of1 μg/ml and 2 μg/ml, respectively against both species.Norfloxacin was less effective against both species at16 and 32 μg/ml. Ciprofloxacin was unusual in thatthe MIC50S varied fourfold between species, with 2 μg/ml against M. hominis and 8 μg/ml against U.urealyticum.Conclusions: The results can provide useful infor-mation for selecting fluoroquinolones for treatmentof urogenital mycoplasma infections.
文摘\ 2Alkyl6oxo8fluoro9(4methylpiperazin1yl)6Himidazo(4,5,1ij)quinoline5carboxylic acids (2Ab～2Ae) were prepared by condensation of ethyl 6fluoro7(4methylpiperazin1yl)8amino1,4dihydro4oxo3quinolinecarboxylate (5A) with the aliphatic acids in PPA. Other target compounds 2Af～2Ah, 2Bc, 2Cc, 2Aa～2Da, 2Bi and 2Ci were prepared by the condensation of 6fluoro7nitrogencontaining heterocycle8amino1,4dihydro4oxo3quinolinecarboxylic acids (9A～9D) with the corresponding acids in PPA or with ethyl orthoformate or by the diazotisation of 9B and 9C, respectively. Only 2Ab and 2Ac showed moderate antibacterial activity in in vitro test.
基金the National Basic Research Program of China,No. 2004BC518902
文摘AIM： To study the relationship between quantitative structure and pharmacokinetics （QSPkR） of fluorocluinolone antibacterials.METHODS： The pharmacokinetic （PK） parameters of oral fluoroquinolones were collected from the literature. These pharmacokinetic data were averaged, 19 compounds were used as the training set, and 3 served as the test set. Genetic function approximation （GFA） module of Cerius2 software was used in QSPkR analysis.RESULTS： A small volume and large polarizability and surface area of substituents at C-7 contribute to a large area under the curve （AUC） for fluoroquinolones. Large polarizability and small volume of substituents at N-1 contribute to a long half life elimination.CONCLUSION： QSPkR models can contribute to some fluoroquinolones antibacterials with excellent pharmacokinetic properties.
基金Project supported by the National Natural Science Foundation of China (Nos.20375035 and 20527005)the Natural Science Foundation of Zhejiang Province (No.Z404105), China
文摘For preparing fluorinated quinolone antibiotic medicine locally used in stomatology, simultaneous determination of norfloxacin, ciprofloxacin, and enoxacin was carried out by multiphase ion chromatography with fluorescence detection. Quinolone antibiotics were separated by Dionex OmniPac PAX-500 column with an eluent of 15 mmol/L H2SO4 and 35% methanol （v/v） at a flow-rate of 1.0 ml/min and detected with fluorescence with excitation and emission wave lengths of 347 ran and 420 ran respectively. The detection limits （S/N=3） of norfloxacin, ciprofloxacin and enoxacin were 50, 105 and 80 ng/ml respectively. The relative standard deviations of retention time, peak area and peak height were less than 1.1% and good linear relationship resulted. The developed method was applied to pharmaceutical formulations and biological fluids.
文摘AIM:To compare triple therapy vs quadruple therapy for 10 d as first-line treatment ofHelicobacter pylori(H.pylori) infection.METHODS:Consecutive H.pylori positive patients never treated in the past for this infection were randomly treated with triple therapy of pantoprazole(PAN) 20 mg bid,amoxicillin(AMO) 1 g bid and moxifloxacin(MOX) 400 mg bid for 10 d(PAM) or with quadruple therapy of PAN 20 mg bid,AMO 1 g bid,MOX 400 mg bid and bismuth subcitrate 240 mg bid for 10 d(PAMB).All patients were found positive at 13 C-Urea breath test(UBT) performed within ten days prior to the start of the study.A successful outcome was confirmed with an UBT performed 8 wk after the end of treatment.χ 2 analysis was used for statistical comparison.Per protocol(PP) and intention-to-treat(ITT) values were also calculated.RESULTS:Fifty-seven patients were enrolled in the PAM group and 50 in the PAMB group.One patient in each group did not return for further assessment.Eradication was higher in the PAMB group(negative:46 and positive:3) vs the PAM group(negative:44 and positive:12).The H.pylori eradication rate was statistically significantly higher in the PAMB group vs the PAM group,both with the PP and ITT analyses(PP:PAMB 93.8%,PAM 78.5%,P < 0.02;ITT:PAMB 92%,PAM 77.1 %,P <0.03).CONCLUSION:The addition of bismuth subcitrate can be considered a valuable adjuvant to triple therapy in those areas where H.pylori shows a high resistance to fluoroquinolones.
文摘According to a review article by Biecker et al published in a previous issue of World Journal of Gastroenterology in March 2011,intestinal decontamination with norfloxacin remains the mainstay of primary prophylaxis of spontaneous bacterial peritonitis(SBP) at the expense of development of quinolone-resistant bacteria after long-term use.In our research,the administration of a 4-wk regimen with rifaximin 1200 mg/d reduced significantly the ascitic neutrophil count in cirrhotic patients with sterile ascites in line with a significant decrease in plasma endotoxin levels.Our observations concur with recent findings,showing a significantly reduced 5-year probability of SBP in cirrhotic patients taking rifaximin.
文摘OBJECTIVE: To study the resistance mechanism of clinical isolates of Ureaplasma urealyticum resistant to fluoroquinolones. METHODS: Thirteen isolates of Ureaplasma urealyticum resistant to six fluoroquinolones were selected out of 184 clinical isolates and their QRDRs (quinolone resistance-determining region) gyrA, gyrB, parC and parE were amplified by PCR. Sequencing results were compared to those susceptible reference strains and a comparison of deduced amino acid sequences were performed. RESULTS: Sequence comparison revealed a C to A change at 87nt of gyrA QRDR leading to the substitution of Asp95 with glutamic acid and a C to T change at 50nt of parC QRDR leading to the substitution of Ser80 with leucine. CONCLUSION: These results suggest that a C to A change at 87nt of gyrA QRDR and a C to T change at 50nt of parC QRDR are associated with fluoroquinolone resistance of Ureaplasma urealyticum.
文摘Objective To evaluate the role of outer membrane protein (Omp) F-deficiency and active efflux in the accumulation of hydrophilic fluoroquinolones ciprofloxacin (CPLX) and lomefloxacin (LMLX) in resistant E. coli strains. Methods Fluoroquinolone accumulation in bacteria and the effect of active efflux were measured by a fluorescence method. The outer membrane proteins of the bacteria were analysed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). E. coli strains in this study included control strains JF701 and JF703 that are OmpC- or OmpF-deficient mutants of E. coli K-12, respectively, and the fluoroquinolone susceptible strain the fluoroquinolone susceptible strain of Escherichia coli (Ecs) and its in vitroselected resistant strains R2 and R256, and the clinical resistant isolates R5 and R6. Results The steady-state accumulation concentration of each drug in Ecs appeared to be the same as in JF701, while in the OmpF- deficient strain JF703, it was 1/5 CPLX or 1/2 LMLX lower than that in JF701, but JF703 was still susceptible to fluoroquinolones. On the other hand, compared with susceptible strains, a 2- to 10-fold decrease in the accumulation of each drug was found in the resistant strains except R2, in which the accumulation was slightly higher than in JF703. After the addition of 2,4-dinitrophenol (DNP), accumulation of each drug increased, especially in resistant strains, indicating that the function of the active efflux (pump) system in these bacteria had been enhanced dramatically. Furthermore, both OmpF and OmpC in Ecs, OmpF-deficiency in R2 and R256 and OmpC-deficiency in R5 and R6 were observed.Conclusion The decreased accumulation of hydrophilic fluoroquinolones in E. coli involved OmpF-deficiency and active efflux (pump), and the latter may be an important factor.
基金ThisstudywassupportedbyagrantfromtheEducationCommitteeofHunanProvince (No 0 0A0 0 9)
文摘To study the resistance mechanism of clinical isolates of Ureaplasma urealyticum resistant to fluoroquinolones Methods Thirteen isolates of Ureaplasma urealyticum resistant to six fluoroquinolones were selected out of 184 clinical isolates and their QRDRs (quinolone resistance determining region) gyrA, gyrB, parC and parE were amplified by PCR Sequencing results were compared to those susceptible reference strains and a comparison of deduced amino acid sequences were performed Results Sequence comparison revealed a C to A change at 87nt of gyrA QRDR leading to the substitution of Asp95 with glutamic acid and a C to T change at 50nt of parC QRDR leading to the substitution of Ser80 with leucine Conclusion These results suggest that a C to A change at 87nt of gyrA QRDR and a C to T change at 50nt of parC QRDR are associated with fluoroquinolone resistance of Ureaplasma urealyticum
基金supported by the National Natural Science Foundation of China (21173252)
文摘The reactions between gatifloxacin(GFX) and various one-electron oxidants,such as ˙OH,N3˙,Br2˙ˉ,and SO4˙ˉ,have been studied by pulse radiolysis techniques.The GFX radical anion formed in the reaction of GFX with eaqˉ could either be protonated or deprotonated,and the absorption of GFX radical anion was located at 390 nm.The transient species produced by the reaction of GFX with ˙OH radical shows a broad band in the 380?600 nm region with a shoulder,while the oxidation by N3˙,SO4˙ˉ,and Br2˙ˉ results in an absorption band with λmax = 370 nm.At neutral condition(pH 7),the rate constants of GFX reacting with ˙OH,N3˙,Br2˙ˉ,SO4˙ˉ and eaqˉ are estimated to be 1.0 × 1010,3.1 × 109,2.8 × 109,3.0 × 109,and 1.8 × 1010 dm3 mol?1 s?1,respectively.From the pH dependence on the formation of electron adducts and on the rate constant of GFX with eaqˉ,the pKa of GFX radical anion is estimated to be 5.5 and 9.3.
