Staphylococci strains, like the majority of bacterial strains, have developed the resistance to several antibiotics, including Quinolones and Fluoroquin-olones In the Republic of the Congo, cases of resistance leading...Staphylococci strains, like the majority of bacterial strains, have developed the resistance to several antibiotics, including Quinolones and Fluoroquin-olones In the Republic of the Congo, cases of resistance leading to treat-ment failures have been observed during the treatment of staphylococcal infections with antibiotics in hospitals. The objective of this study was to identify the Quinolone/Fluoroquinolone resistance genes from staphylo-cocci strains isolated in hospitals. A total of 51 strains of Staphylococci were isolated, including 16 (31.37%) community strains, and 35 (68.62%) clinical strains. 46 strains of Staphylococcus aureus (S. aureus) and 5 SCNs were identified. A total of 34 DNA fragments from different strains resistant to Quinolones/Fluoroquinolones, including 21 (61.67%) DNA fragments from clinical S. aureus and 13 (38.23%) from community SCN strains were analyzed by the molecular method (genotypic detection) by PCR. The genotypic results made it possible to identify the gyrA, grLA and norA genes and to show that these genes are involved in the resistance of the strains to the various antibiotics used. The grLA gene was the most identified gene with a frequency of 75%. The gyrA and grLA genes have been identified in Staphylococcus aureus and Coagulase Negative Staphy-lococci. The norA gene, on the other hand, has only been identified in Staphylococcus aureus. Two mechanisms are essentially involved in the resistance of Staphylococci to quinolones/Fluoroquinolones, the mecha-nism of resistance by efflux, which takes place thanks to a transmembrane protein coded by the norA gene and by point mutations (substitution and deletion of acids or nucleotides) observed within the protein and nucleic sequences of the chromosomal gyrA and grLA genes.展开更多
Several 6,8-dichloroquinolone analogues were synthesized from the key intermediate compound of 2,3,4,5-tetrachlorobenzene carbonyl chloride, which was obtained from the starting material of tetrachlorophthalic anhydri...Several 6,8-dichloroquinolone analogues were synthesized from the key intermediate compound of 2,3,4,5-tetrachlorobenzene carbonyl chloride, which was obtained from the starting material of tetrachlorophthalic anhydride. Their in vitro antibacterial activities were evaluated. As a result of this study, compounds 21e and 21d were twofold more potent than ciprofloxacin （CPFX） and norfloxacin （NFLX） against Staphylococcus aureus-9, and with the same potent as CPFX and NFLX while against Escherichia coli-2, but were less potent than references in against Pseudomonas aeruginosa-17.展开更多
Quinolone has a broad spectrum of synthetic antibiotics with a strong therapeutic effect and quinolone is a term used for chemical treatments used to treat a powerful bacteria.Quinolones are divided into 4 generations...Quinolone has a broad spectrum of synthetic antibiotics with a strong therapeutic effect and quinolone is a term used for chemical treatments used to treat a powerful bacteria.Quinolones are divided into 4 generations according to the bacterial spectrum,the majority of quinolones used clinically belong to the sub fluoroquinolones group,which has a fluorine atom linked to the central ring system,usually on its carbon atom 6 or 7.Herein in this article,six new nickel(Ⅱ)complexes(Ⅰ—Ⅵ)have been synthesized in aqueous alkaline media at pH ranged 8-9,the chemical reactions take place between levofloxacin(HLEV),lomefloxacin(HLOM),nalidixic acid(HNLA),oxolonic acid(HOXO),pipemidic acid(HPIP),and pefloxacin mesylate(HPEF)with nickel(Ⅱ)nitrate hexahydrate.The microanalytical(percentage of carbon,hydrogen and nitrogen),molar conductance(Λm),Infrared(FTIR)spectra,electronic(UV-Vis)spectra,and effective magnetic moment instrumentals were used to identify the suggested structures and their surface morphology.According the analytical and spectroscopic analyses,the stoichiometry between nickel(Ⅱ)metal ion and drug ligands was found to be 1∶2 with general formula as[Ni(L)_(2)(H_(2)O)_(2)]·x H_(2)O(L=LEV(Ⅰ),LOM(Ⅱ),NAL(Ⅲ),OXO(Ⅳ),PIP(V),and PEF(Ⅵ);x=2 or 4).By the comparison between FTIR spectra of quinolone drugs and their complexes,it can be deduced that all the drug ligands act as a bidentate chelates through oxygen atoms of pyridine ring and carboxylate group.The electronic configuration of all synthesized nickel(Ⅱ)complexes were octahedral geometry which confirmed based on the values of magnetic susceptibility and the electronic transition bands.展开更多
<strong>Background:</strong> Enterobacteriaceae causes many types of infections which are often treated with quinolones and fluoroquinolone (Q/FQ). The resistance mechanisms to Q/FQ are usually associated ...<strong>Background:</strong> Enterobacteriaceae causes many types of infections which are often treated with quinolones and fluoroquinolone (Q/FQ). The resistance mechanisms to Q/FQ are usually associated with mutations in the quinolone resistance determining region which alter the conformation of target amino acid residues within the protein and in the <em>qnr</em> genes. This study aimed at determining the antimicrobial resistant profile of a sample of Enterobacteriaceae from Cameroon and the genetic diversity in quinolone-resistant isolates in view of implementing a better management, treatment, control and prevention of the transmission of these resistant strains. <strong>Methods:</strong> Identification and antimicrobial susceptibility testing was done using VITEK 2. The detection of plamid-mediated quinolone resistance (PMQR) genes was carried out using the conventional PCR method. Sequencing was done using the Applied Biosystem 3500 genetic analyser. DNA fingerprint was obtained using Pulsed-Field Gel electrophoresis. <strong>Results:</strong> Among 440 Enterobacteriaceae, the most prevalent genera were: <em>Escherichia</em> 178/440 (39.5%);<em>Klebsiella</em> 148/440 (33.6%);<em>Enterobacter </em>35/440 (8%);<em>Pantoea</em> 28/440 (6.4%);<em>Proteus</em> 14/440 (3.2%) <em>Salmonella </em>13/440 (3%). Ampicillin resistance showed the highest prevalence with 371/440 (81%) and Imipenem the lowest resistance 9/440 (2.1%). The ciprofloxacin resistance rate was 161/440 (36.6%). The detected plasmid mediated quinolone resistance (PMQR) genes were: <em>qnrA</em>, 2/161 (1.2%);<em>qnrB</em>, 31/161 (19.3%);<em>qnrS</em>, 13/161 (8.1%): <em>Aac</em> (6')<em>Ib-cr</em>, 84/161 (52.2%) and <em>qepA</em>, 3/161 (1.9%). There were several mutations in the <em>parC</em> gene of <em>Klebsiella</em> leading to S80D and S80N substitutions. Two pairs of <em>Klebsiella</em> <em>peumoniae</em> strains were phenotypically and genotypically identical with 100% similarity in the dendrogramme. <strong>Conclusion:</strong> This study showed that quinolone resistance was high. The PMQR genes contributing to this resistance were diverse. This high PMQR indicates that there has been an unknown circulation of these genes in our community. To avoid the rapid dissemination of these PMQR genes continuous surveillance of antimicrobial resistance should be carried out not only in humans but also in animals to monitor the evolution of these genes.展开更多
AIM:To investigate the resistance of Helicobacter pylori(H.pylori) to ciprofloxacin(CIP),levofloxacin(LVX) and moxifloxacin(MOX) in the Beijing area and to elucidate the resistance mechanisms.METHODS:Seventy-nine H.py...AIM:To investigate the resistance of Helicobacter pylori(H.pylori) to ciprofloxacin(CIP),levofloxacin(LVX) and moxifloxacin(MOX) in the Beijing area and to elucidate the resistance mechanisms.METHODS:Seventy-nine H.pylori clinical strains,isolated from patients who had undergone upper gastrointestinal endoscopy in Peking University First Hospital from 2007 to 2009,were tested for their susceptibility to CIP,LVX and MOX using the E-test method.H.pylori strain 26695 was included in the susceptibility testing as a control strain.According to the minimal inhibitory concentration(MIC) values,a strain was classified as resistant to CIP,LVX or MOX when the MIC was > 1 μg/mL.We amplified by polymerase chain reaction(PCR) and sequenced the quinolone resistance-determining regions of the gyrA and gyrB genes from 29 quinolone-resistant and 16 quinolone-susceptible H.pylori strains selected at random.RESULTS:In this study,the resistance rates of H.pylori to CIP,LVX or MOX were 55.7%(44/79),and the primary resistance rates were 26.6%(21/79).Patients with secondary resistance had received LVX in previous eradication treatments,but not MOX or CIP.Forty-five strains,including 29 CIP,LVX or MOX-resistant strains(MIC:1.5-32 μg/mL) and 16 susceptible strains,were selected randomly from the 79 strains and used in PCR analysis.Among these 45 strains,27 resistant strains had mutations in the gyrA gene,including 11 strains with mutations corresponding to Asp-91(MIC:2-32 μg/mL),one of which also had a mutation corresponding to Val-150,and 16 strains had mutations at Asn-87(MIC:4-32 μg/mL),three of which also had mutations corresponding to Arg-140 or Val-150.In addition,Arg-140,Val-150 or Ala-97 mutations were separately detected in three susceptible strains.Analysis of the gyrB gene showed that one strain of low resistance had a mutation corresponding to Ser-457 that coexisted with an Asp-91 mutation.There was a significant difference in the occurrence of mutations in the gyrA gene between CIP,LVX and MOX-resistant and-susceptible strains(P < 0.05),but 2 resistant strains were found to possess no quinolone resistance-determining region mutations.CONCLUSION:Resistance is primarily mediated through point mutations in gyrA.Whether other mechanisms are responsible for resistance in strains without mutations in the QRDR should be detected.展开更多
A novel method for the determination of two quinolone drugs norfloxacin （NOR） and levofloxacin （LVX） was described by capillary electrophoresis with electrochemiluminescence detection. The good relationship （r ≥...A novel method for the determination of two quinolone drugs norfloxacin （NOR） and levofloxacin （LVX） was described by capillary electrophoresis with electrochemiluminescence detection. The good relationship （r ≥ 0.9991） between peak area and concentration of analytes was established over two orders of magnitude. The limits of detection （LOD, S/N = 3） in standard solution are 4.8 × 10^-7 mol/L for NOR and 6.4 × 10^-7 mol/L for LVX, respectively. The limits of quantitation （LOQ, S/N = 10） in real human urine samples are 1.2 × 10^-6 mol/L for NOR and 1.4 × 10^-6 mol/L for LVX, respectively. The present method was successfully applied to the determination of NOR and LVX in human urine and the studv of oharmacokinetics of NOR.展开更多
This study surveyed 180 samples of ultra high temperature （UHT） milk of four top Chinese dairy brands collected in the 25 cities in China in June 2011, and assessed their contamination with antibiotics, using the EL...This study surveyed 180 samples of ultra high temperature （UHT） milk of four top Chinese dairy brands collected in the 25 cities in China in June 2011, and assessed their contamination with antibiotics, using the ELISA method. The percentages of tetracyclines, sulfonamides, sulfamethazine, and quinolones detected in the samples were 0, 16.7, 40.6, and 100%, respectively. The maximum concentrations of the tetracyclines, sulfonamides, sulfamethazine and quinolones in UHT milk samples were 〈1.5, 26.2, 22.6, and 58.8 μg kg-1, respectively. None of the samples exceeded the maximum residue levels （MRLs） for these four veterinary drugs, according to the regulations set by China, the European Union （EU） and the Codex Alimentarius Commission （CAC）.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
In this study,6-chloro-4-hydroxy-2-quinolone and 6-flouro-4-hydroxy-2-quinolone were synthesized from corresponding dianilides.These compounds were coupled with some diazotized aromatic amines to give the correspondin...In this study,6-chloro-4-hydroxy-2-quinolone and 6-flouro-4-hydroxy-2-quinolone were synthesized from corresponding dianilides.These compounds were coupled with some diazotized aromatic amines to give the corresponding azo disperse dyes.The structures of the quinolone derivatives and new azo dyes were confirmed by UV-vis,FT-IR,;H NMR and elemental analysis.展开更多
AIM To assess the efficacy and safety of fourth-generation quinolones for helicobacter pylori(h. pylori) eradication, we conducted this systematic review and metaanalysis of randomized clinical trials. METHODS Major l...AIM To assess the efficacy and safety of fourth-generation quinolones for helicobacter pylori(h. pylori) eradication, we conducted this systematic review and metaanalysis of randomized clinical trials. METHODS Major literature databases(Pub Med, EMBASE and the Cochrane Central Register of Controlled Trials) were searched for relevant articles published prior to February 2018. We performed a meta-analysis of all randomized clinical trials that examined the efficacy of h. pylori eradication therapies and included fourthgeneration quinolones in the experimental arm. Subgroup analyses by regions and different types of fourth-generation quinolones were also performed.RESULTS Ten studies including a total of 2198 patients were assessed. A meta-analysis of randomized controlled trials showed that the eradication rate of therapies containing non-fourth-generation quinolones was significantly lower than that of therapies containing fourth-generation quinolones by intention-to-treat(ITT) analysis [75.4% vs 81.8%; odds ratio(OR) = 0.661; 95% confidence interval(CI): 0.447-0.977; P = 0.038]. This analysis also showed that the eradication rate of the therapies containing non-fourth-generation quinolones was inferior to that of therapies containing fourth-generation quinolones by perprotocol analysis(79.1% vs 84.7%; OR = 0.663; 95%CI: 0.433-1.016; P = 0.059). Moreover, the occurrence of side effects was significantly different between the control and experimental groups by ITT analysis(30.6% vs 19.5%; OR = 1.874; 95%CI: 1.120-3.137; P = 0.017). The sub-analyses also showed significant differences in moxifloxacin therapies vs other fourth-generation quinolone therapies(84.3% vs 71.9%) and in Asian vs European groups(76.7% vs 89.1%).CONCLUSION Therapies containing fourth-generation quinolones achieved a poor eradication rate in the treatment of h. pylori infection. Such regimens might be useful as a rescue treatment based on antimicrobial susceptibility testing. Different antibiotics should be chosen in different regions.展开更多
7-[4-（Aminomethyl）-3-（methoxyimino）pyrrolidin- 1-yl]- 1-cyclopropyl-6-fluoro-8-difluoromethoxy- 1,4-dihydro-4-oxoquino- line-3-carboxylic acid and its analogues have been prepared and evaluated for antibacterial a...7-[4-（Aminomethyl）-3-（methoxyimino）pyrrolidin- 1-yl]- 1-cyclopropyl-6-fluoro-8-difluoromethoxy- 1,4-dihydro-4-oxoquino- line-3-carboxylic acid and its analogues have been prepared and evaluated for antibacterial activity in vitro.展开更多
New quinolone derivatives of 7-[2-aminomethylaziridin-l-yl]quinolone-3-carboxylic acids were synthesized. The structures of these compounds were characterized by IH NMR and HRESI-MS.
A series of quinolone derivatives containing benzimidazole, benzoxazole or benzothiazole ring were synthesized. The cytotoxicity of 12 new compounds was evaluated in KB, Be17402, A2780 and HT-29 cell lines. Most of sy...A series of quinolone derivatives containing benzimidazole, benzoxazole or benzothiazole ring were synthesized. The cytotoxicity of 12 new compounds was evaluated in KB, Be17402, A2780 and HT-29 cell lines. Most of synthesized compounds showed moderate inhibitory activity against cancer cells. The inhibitory activities of 6k, against KB and A2780 tumor ceils are comparable to that of topotecan, one of topoisomerase I inhibitors.展开更多
The accelerated weight gain in productive animals as a result of feeding antibiotic enriched fodder has been well known for decades. The better energy harvest is the result of modified gut microbiota as a consequence ...The accelerated weight gain in productive animals as a result of feeding antibiotic enriched fodder has been well known for decades. The better energy harvest is the result of modified gut microbiota as a consequence of applied antibiotics. Similar mechanisms might result obesity in humans as well. Objectives: Finding associations between global antibiotic consumption of different classes in EU countries and obesity data in adults and children prove that antibiotics might play a significant role in the development of obesity “epidemics” and related illnesses. Methods: Antibiotic consumption data were compared with obesity figures in adults and children in European countries and statistically analyzed for significance. Results: Significant correlation was found between the average yearly consumption of cephalosporins (p = 0.007), quinolones (p = 0.031), macrolides (p = 0.000083) and childhood obesity data, but no significant association was observed with the average penicillin consumption. No association was observed between adult obesity and any of the antibiotic classes studied. Conclusions: Our results support the hypothesis that different types of antibiotics might influence the development of obesity among children, and this finding can serve as a unified explanation for the development of obesity “epidemics”, similarly to the obesity and gut flora alteration-related diseases (type 2 diabetes mellitus, autism, etc.).展开更多
MicroRNA-21(miRNA-21)is highly expressed in various tumors.Small-molecule inhibition of miRNA-21 is considered to be an attractive novel cancer therapeutic strategy.In this study,fluoroquinolone derivatives A1eA43 wer...MicroRNA-21(miRNA-21)is highly expressed in various tumors.Small-molecule inhibition of miRNA-21 is considered to be an attractive novel cancer therapeutic strategy.In this study,fluoroquinolone derivatives A1eA43 were synthesized and used as miRNA-21 inhibitors.Compound A36 showed the most potent inhibitory activity and specificity for miRNA-21 in a dual-luciferase reporter assay in HeLa cells.Compound A36 significantly reduced the expression of mature miRNA-21 and increased the protein expression of miRNA-21 target genes,including programmed cell death protein 4(PDCD4)and phosphatase and tensin homology deleted on chromosome ten(PTEN),at 10 μM in HeLa cells.The Cell Counting Kit-8 assay(CCK-8)was used to evaluate the antiproliferative activity of A36;the results showed that the IC_(50) value range of A36 against six tumor cell lines was between 1.76 and 13.0 μM.Meanwhile,A36 did not display cytotoxicity in BEAS-2B cells(lung epithelial cells from a healthy human donor).Furthermore,A36 significantly induced apoptosis,arrested cells at the G_(0)/G_(1) phase,and inhibited cell-colony formation in HeLa cells.In addition,mRNA deep sequencing showed that treatment with A36 could generate 171 dysregulated mRNAs in HeLa cells,while the expression of miRNA-21 target gene dual-specificity phosphatase 5(DUSP5)was significantly upregulated at both the mRNA and protein levels.Collectively,these findings demonstrated that A36 is a novel miRNA-21 inhibitor.展开更多
The derivatives of 4-alkyl-2-quinolones possess a variety of biological activities. The general synthetic method of 4-alkyl-2-quinolones is the reaction of aryl amines with β-ketoesters to form β-ketoamides, which a...The derivatives of 4-alkyl-2-quinolones possess a variety of biological activities. The general synthetic method of 4-alkyl-2-quinolones is the reaction of aryl amines with β-ketoesters to form β-ketoamides, which are then heated in concentrated sulfuric acid to complete the ring closure. Although a number of its 4-methyl and aryl derivatives have been obtained, other 4-alkyl-2-quinolones are rarely mentioned for lack of a convenient method to prepare the appropriate β-ketoesters used in condensation.展开更多
New quinolone derivatives of 7-[(2S, 4R)-2-aminomethyl-4-hydroxypyrrolidin-1-yl] quinolone-3-carboxylic acids were synthesized by condensation of 7-halo substituted quinolone- 3-carboxylic acids with (2S, 4R)-2-aminom...New quinolone derivatives of 7-[(2S, 4R)-2-aminomethyl-4-hydroxypyrrolidin-1-yl] quinolone-3-carboxylic acids were synthesized by condensation of 7-halo substituted quinolone- 3-carboxylic acids with (2S, 4R)-2-aminomethyl-4-hydroxypyrrolidine. These compounds were characterized by FAB-MS and 1H NMR.展开更多
A shake-flask method was used to determine 1-octanol/water partition coefficients of ofloxacin, norfloxacin, lomefloxacin, ciprofloxacin, pefloxacin and pipemidic acid from 293.15 K to 323.15 K. The results show that ...A shake-flask method was used to determine 1-octanol/water partition coefficients of ofloxacin, norfloxacin, lomefloxacin, ciprofloxacin, pefloxacin and pipemidic acid from 293.15 K to 323.15 K. The results show that 1-octanol/water partition coefficient of each quinolone increased with the increase of temperature. Based on the fluid phase equilibrium theory, the thermodynamic relationship of 1-octanol/water partition coefficient depending on the temperature was proposed, and the changes of enthalpy, entropy, and Gibbs free energy for quinolones partitioning in 1-octanol/water were determined, respectively. Quinolones molecules partitioning in 1-octanol/water was mainly an entropy driving process, during which the order degree of system decreased. The temperature effects of 1-octanol/water partition coefficient were investigated. The results show that its magnitude is the same as the values in the literature.展开更多
文摘Staphylococci strains, like the majority of bacterial strains, have developed the resistance to several antibiotics, including Quinolones and Fluoroquin-olones In the Republic of the Congo, cases of resistance leading to treat-ment failures have been observed during the treatment of staphylococcal infections with antibiotics in hospitals. The objective of this study was to identify the Quinolone/Fluoroquinolone resistance genes from staphylo-cocci strains isolated in hospitals. A total of 51 strains of Staphylococci were isolated, including 16 (31.37%) community strains, and 35 (68.62%) clinical strains. 46 strains of Staphylococcus aureus (S. aureus) and 5 SCNs were identified. A total of 34 DNA fragments from different strains resistant to Quinolones/Fluoroquinolones, including 21 (61.67%) DNA fragments from clinical S. aureus and 13 (38.23%) from community SCN strains were analyzed by the molecular method (genotypic detection) by PCR. The genotypic results made it possible to identify the gyrA, grLA and norA genes and to show that these genes are involved in the resistance of the strains to the various antibiotics used. The grLA gene was the most identified gene with a frequency of 75%. The gyrA and grLA genes have been identified in Staphylococcus aureus and Coagulase Negative Staphy-lococci. The norA gene, on the other hand, has only been identified in Staphylococcus aureus. Two mechanisms are essentially involved in the resistance of Staphylococci to quinolones/Fluoroquinolones, the mecha-nism of resistance by efflux, which takes place thanks to a transmembrane protein coded by the norA gene and by point mutations (substitution and deletion of acids or nucleotides) observed within the protein and nucleic sequences of the chromosomal gyrA and grLA genes.
文摘Several 6,8-dichloroquinolone analogues were synthesized from the key intermediate compound of 2,3,4,5-tetrachlorobenzene carbonyl chloride, which was obtained from the starting material of tetrachlorophthalic anhydride. Their in vitro antibacterial activities were evaluated. As a result of this study, compounds 21e and 21d were twofold more potent than ciprofloxacin （CPFX） and norfloxacin （NFLX） against Staphylococcus aureus-9, and with the same potent as CPFX and NFLX while against Escherichia coli-2, but were less potent than references in against Pseudomonas aeruginosa-17.
基金the deanship of scientific Research at Princess Nourah bint Abdulrahman University through the Fast-track Research Funding program。
文摘Quinolone has a broad spectrum of synthetic antibiotics with a strong therapeutic effect and quinolone is a term used for chemical treatments used to treat a powerful bacteria.Quinolones are divided into 4 generations according to the bacterial spectrum,the majority of quinolones used clinically belong to the sub fluoroquinolones group,which has a fluorine atom linked to the central ring system,usually on its carbon atom 6 or 7.Herein in this article,six new nickel(Ⅱ)complexes(Ⅰ—Ⅵ)have been synthesized in aqueous alkaline media at pH ranged 8-9,the chemical reactions take place between levofloxacin(HLEV),lomefloxacin(HLOM),nalidixic acid(HNLA),oxolonic acid(HOXO),pipemidic acid(HPIP),and pefloxacin mesylate(HPEF)with nickel(Ⅱ)nitrate hexahydrate.The microanalytical(percentage of carbon,hydrogen and nitrogen),molar conductance(Λm),Infrared(FTIR)spectra,electronic(UV-Vis)spectra,and effective magnetic moment instrumentals were used to identify the suggested structures and their surface morphology.According the analytical and spectroscopic analyses,the stoichiometry between nickel(Ⅱ)metal ion and drug ligands was found to be 1∶2 with general formula as[Ni(L)_(2)(H_(2)O)_(2)]·x H_(2)O(L=LEV(Ⅰ),LOM(Ⅱ),NAL(Ⅲ),OXO(Ⅳ),PIP(V),and PEF(Ⅵ);x=2 or 4).By the comparison between FTIR spectra of quinolone drugs and their complexes,it can be deduced that all the drug ligands act as a bidentate chelates through oxygen atoms of pyridine ring and carboxylate group.The electronic configuration of all synthesized nickel(Ⅱ)complexes were octahedral geometry which confirmed based on the values of magnetic susceptibility and the electronic transition bands.
文摘<strong>Background:</strong> Enterobacteriaceae causes many types of infections which are often treated with quinolones and fluoroquinolone (Q/FQ). The resistance mechanisms to Q/FQ are usually associated with mutations in the quinolone resistance determining region which alter the conformation of target amino acid residues within the protein and in the <em>qnr</em> genes. This study aimed at determining the antimicrobial resistant profile of a sample of Enterobacteriaceae from Cameroon and the genetic diversity in quinolone-resistant isolates in view of implementing a better management, treatment, control and prevention of the transmission of these resistant strains. <strong>Methods:</strong> Identification and antimicrobial susceptibility testing was done using VITEK 2. The detection of plamid-mediated quinolone resistance (PMQR) genes was carried out using the conventional PCR method. Sequencing was done using the Applied Biosystem 3500 genetic analyser. DNA fingerprint was obtained using Pulsed-Field Gel electrophoresis. <strong>Results:</strong> Among 440 Enterobacteriaceae, the most prevalent genera were: <em>Escherichia</em> 178/440 (39.5%);<em>Klebsiella</em> 148/440 (33.6%);<em>Enterobacter </em>35/440 (8%);<em>Pantoea</em> 28/440 (6.4%);<em>Proteus</em> 14/440 (3.2%) <em>Salmonella </em>13/440 (3%). Ampicillin resistance showed the highest prevalence with 371/440 (81%) and Imipenem the lowest resistance 9/440 (2.1%). The ciprofloxacin resistance rate was 161/440 (36.6%). The detected plasmid mediated quinolone resistance (PMQR) genes were: <em>qnrA</em>, 2/161 (1.2%);<em>qnrB</em>, 31/161 (19.3%);<em>qnrS</em>, 13/161 (8.1%): <em>Aac</em> (6')<em>Ib-cr</em>, 84/161 (52.2%) and <em>qepA</em>, 3/161 (1.9%). There were several mutations in the <em>parC</em> gene of <em>Klebsiella</em> leading to S80D and S80N substitutions. Two pairs of <em>Klebsiella</em> <em>peumoniae</em> strains were phenotypically and genotypically identical with 100% similarity in the dendrogramme. <strong>Conclusion:</strong> This study showed that quinolone resistance was high. The PMQR genes contributing to this resistance were diverse. This high PMQR indicates that there has been an unknown circulation of these genes in our community. To avoid the rapid dissemination of these PMQR genes continuous surveillance of antimicrobial resistance should be carried out not only in humans but also in animals to monitor the evolution of these genes.
基金Supported by A Grant from the Beijing Medicine Researchand Development Fund,No 2005-1008
文摘AIM:To investigate the resistance of Helicobacter pylori(H.pylori) to ciprofloxacin(CIP),levofloxacin(LVX) and moxifloxacin(MOX) in the Beijing area and to elucidate the resistance mechanisms.METHODS:Seventy-nine H.pylori clinical strains,isolated from patients who had undergone upper gastrointestinal endoscopy in Peking University First Hospital from 2007 to 2009,were tested for their susceptibility to CIP,LVX and MOX using the E-test method.H.pylori strain 26695 was included in the susceptibility testing as a control strain.According to the minimal inhibitory concentration(MIC) values,a strain was classified as resistant to CIP,LVX or MOX when the MIC was > 1 μg/mL.We amplified by polymerase chain reaction(PCR) and sequenced the quinolone resistance-determining regions of the gyrA and gyrB genes from 29 quinolone-resistant and 16 quinolone-susceptible H.pylori strains selected at random.RESULTS:In this study,the resistance rates of H.pylori to CIP,LVX or MOX were 55.7%(44/79),and the primary resistance rates were 26.6%(21/79).Patients with secondary resistance had received LVX in previous eradication treatments,but not MOX or CIP.Forty-five strains,including 29 CIP,LVX or MOX-resistant strains(MIC:1.5-32 μg/mL) and 16 susceptible strains,were selected randomly from the 79 strains and used in PCR analysis.Among these 45 strains,27 resistant strains had mutations in the gyrA gene,including 11 strains with mutations corresponding to Asp-91(MIC:2-32 μg/mL),one of which also had a mutation corresponding to Val-150,and 16 strains had mutations at Asn-87(MIC:4-32 μg/mL),three of which also had mutations corresponding to Arg-140 or Val-150.In addition,Arg-140,Val-150 or Ala-97 mutations were separately detected in three susceptible strains.Analysis of the gyrB gene showed that one strain of low resistance had a mutation corresponding to Ser-457 that coexisted with an Asp-91 mutation.There was a significant difference in the occurrence of mutations in the gyrA gene between CIP,LVX and MOX-resistant and-susceptible strains(P < 0.05),but 2 resistant strains were found to possess no quinolone resistance-determining region mutations.CONCLUSION:Resistance is primarily mediated through point mutations in gyrA.Whether other mechanisms are responsible for resistance in strains without mutations in the QRDR should be detected.
基金the National Natural Science Foundation of China(No.20575056)Henan Innovation Project for University Research Talents(No.2005126).
文摘A novel method for the determination of two quinolone drugs norfloxacin （NOR） and levofloxacin （LVX） was described by capillary electrophoresis with electrochemiluminescence detection. The good relationship （r ≥ 0.9991） between peak area and concentration of analytes was established over two orders of magnitude. The limits of detection （LOD, S/N = 3） in standard solution are 4.8 × 10^-7 mol/L for NOR and 6.4 × 10^-7 mol/L for LVX, respectively. The limits of quantitation （LOQ, S/N = 10） in real human urine samples are 1.2 × 10^-6 mol/L for NOR and 1.4 × 10^-6 mol/L for LVX, respectively. The present method was successfully applied to the determination of NOR and LVX in human urine and the studv of oharmacokinetics of NOR.
基金funded by the Ministry of Agriculture of China (2013-Z10)Chinese Academy of Agricultural Sciences (2012ZL071)Institute of Animal Science, Chinese Academy of Agricultural Sciences (2013ywf-yb-4)
文摘This study surveyed 180 samples of ultra high temperature （UHT） milk of four top Chinese dairy brands collected in the 25 cities in China in June 2011, and assessed their contamination with antibiotics, using the ELISA method. The percentages of tetracyclines, sulfonamides, sulfamethazine, and quinolones detected in the samples were 0, 16.7, 40.6, and 100%, respectively. The maximum concentrations of the tetracyclines, sulfonamides, sulfamethazine and quinolones in UHT milk samples were 〈1.5, 26.2, 22.6, and 58.8 μg kg-1, respectively. None of the samples exceeded the maximum residue levels （MRLs） for these four veterinary drugs, according to the regulations set by China, the European Union （EU） and the Codex Alimentarius Commission （CAC）.
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In this study,6-chloro-4-hydroxy-2-quinolone and 6-flouro-4-hydroxy-2-quinolone were synthesized from corresponding dianilides.These compounds were coupled with some diazotized aromatic amines to give the corresponding azo disperse dyes.The structures of the quinolone derivatives and new azo dyes were confirmed by UV-vis,FT-IR,;H NMR and elemental analysis.
基金Supported by the Graduate Innovation Project of Nanchang University,No.CX2017213 and No.CX2017251the National Natural Science Foundation of China,No.81460115the Science and Technology Projects of Jiangxi Province,No.2014BBG70019
文摘AIM To assess the efficacy and safety of fourth-generation quinolones for helicobacter pylori(h. pylori) eradication, we conducted this systematic review and metaanalysis of randomized clinical trials. METHODS Major literature databases(Pub Med, EMBASE and the Cochrane Central Register of Controlled Trials) were searched for relevant articles published prior to February 2018. We performed a meta-analysis of all randomized clinical trials that examined the efficacy of h. pylori eradication therapies and included fourthgeneration quinolones in the experimental arm. Subgroup analyses by regions and different types of fourth-generation quinolones were also performed.RESULTS Ten studies including a total of 2198 patients were assessed. A meta-analysis of randomized controlled trials showed that the eradication rate of therapies containing non-fourth-generation quinolones was significantly lower than that of therapies containing fourth-generation quinolones by intention-to-treat(ITT) analysis [75.4% vs 81.8%; odds ratio(OR) = 0.661; 95% confidence interval(CI): 0.447-0.977; P = 0.038]. This analysis also showed that the eradication rate of the therapies containing non-fourth-generation quinolones was inferior to that of therapies containing fourth-generation quinolones by perprotocol analysis(79.1% vs 84.7%; OR = 0.663; 95%CI: 0.433-1.016; P = 0.059). Moreover, the occurrence of side effects was significantly different between the control and experimental groups by ITT analysis(30.6% vs 19.5%; OR = 1.874; 95%CI: 1.120-3.137; P = 0.017). The sub-analyses also showed significant differences in moxifloxacin therapies vs other fourth-generation quinolone therapies(84.3% vs 71.9%) and in Asian vs European groups(76.7% vs 89.1%).CONCLUSION Therapies containing fourth-generation quinolones achieved a poor eradication rate in the treatment of h. pylori infection. Such regimens might be useful as a rescue treatment based on antimicrobial susceptibility testing. Different antibiotics should be chosen in different regions.
文摘7-[4-（Aminomethyl）-3-（methoxyimino）pyrrolidin- 1-yl]- 1-cyclopropyl-6-fluoro-8-difluoromethoxy- 1,4-dihydro-4-oxoquino- line-3-carboxylic acid and its analogues have been prepared and evaluated for antibacterial activity in vitro.
文摘New quinolone derivatives of 7-[2-aminomethylaziridin-l-yl]quinolone-3-carboxylic acids were synthesized. The structures of these compounds were characterized by IH NMR and HRESI-MS.
基金supported by National Natural Science Foundation of China (No.30271543).
文摘A series of quinolone derivatives containing benzimidazole, benzoxazole or benzothiazole ring were synthesized. The cytotoxicity of 12 new compounds was evaluated in KB, Be17402, A2780 and HT-29 cell lines. Most of synthesized compounds showed moderate inhibitory activity against cancer cells. The inhibitory activities of 6k, against KB and A2780 tumor ceils are comparable to that of topotecan, one of topoisomerase I inhibitors.
文摘The accelerated weight gain in productive animals as a result of feeding antibiotic enriched fodder has been well known for decades. The better energy harvest is the result of modified gut microbiota as a consequence of applied antibiotics. Similar mechanisms might result obesity in humans as well. Objectives: Finding associations between global antibiotic consumption of different classes in EU countries and obesity data in adults and children prove that antibiotics might play a significant role in the development of obesity “epidemics” and related illnesses. Methods: Antibiotic consumption data were compared with obesity figures in adults and children in European countries and statistically analyzed for significance. Results: Significant correlation was found between the average yearly consumption of cephalosporins (p = 0.007), quinolones (p = 0.031), macrolides (p = 0.000083) and childhood obesity data, but no significant association was observed with the average penicillin consumption. No association was observed between adult obesity and any of the antibiotic classes studied. Conclusions: Our results support the hypothesis that different types of antibiotics might influence the development of obesity among children, and this finding can serve as a unified explanation for the development of obesity “epidemics”, similarly to the obesity and gut flora alteration-related diseases (type 2 diabetes mellitus, autism, etc.).
基金Financial support from the National Natural Science Foundation of China(Grant No.:81673354)is gratefully acknowledged.
文摘MicroRNA-21(miRNA-21)is highly expressed in various tumors.Small-molecule inhibition of miRNA-21 is considered to be an attractive novel cancer therapeutic strategy.In this study,fluoroquinolone derivatives A1eA43 were synthesized and used as miRNA-21 inhibitors.Compound A36 showed the most potent inhibitory activity and specificity for miRNA-21 in a dual-luciferase reporter assay in HeLa cells.Compound A36 significantly reduced the expression of mature miRNA-21 and increased the protein expression of miRNA-21 target genes,including programmed cell death protein 4(PDCD4)and phosphatase and tensin homology deleted on chromosome ten(PTEN),at 10 μM in HeLa cells.The Cell Counting Kit-8 assay(CCK-8)was used to evaluate the antiproliferative activity of A36;the results showed that the IC_(50) value range of A36 against six tumor cell lines was between 1.76 and 13.0 μM.Meanwhile,A36 did not display cytotoxicity in BEAS-2B cells(lung epithelial cells from a healthy human donor).Furthermore,A36 significantly induced apoptosis,arrested cells at the G_(0)/G_(1) phase,and inhibited cell-colony formation in HeLa cells.In addition,mRNA deep sequencing showed that treatment with A36 could generate 171 dysregulated mRNAs in HeLa cells,while the expression of miRNA-21 target gene dual-specificity phosphatase 5(DUSP5)was significantly upregulated at both the mRNA and protein levels.Collectively,these findings demonstrated that A36 is a novel miRNA-21 inhibitor.
基金Supported by the National Natural Science Foundation of China
文摘The derivatives of 4-alkyl-2-quinolones possess a variety of biological activities. The general synthetic method of 4-alkyl-2-quinolones is the reaction of aryl amines with β-ketoesters to form β-ketoamides, which are then heated in concentrated sulfuric acid to complete the ring closure. Although a number of its 4-methyl and aryl derivatives have been obtained, other 4-alkyl-2-quinolones are rarely mentioned for lack of a convenient method to prepare the appropriate β-ketoesters used in condensation.
文摘A series of 1-cyclopropyl-5-amino-6-fluoro-8-methoxyquinoline-3-carboxylic acidshave been prepared and evaluated for antibacterial activity in vitro.
文摘New quinolone derivatives of 7-[(2S, 4R)-2-aminomethyl-4-hydroxypyrrolidin-1-yl] quinolone-3-carboxylic acids were synthesized by condensation of 7-halo substituted quinolone- 3-carboxylic acids with (2S, 4R)-2-aminomethyl-4-hydroxypyrrolidine. These compounds were characterized by FAB-MS and 1H NMR.
基金Supported by the Natural Science Foundation of Henan Province,China(No.0611033400)
文摘A shake-flask method was used to determine 1-octanol/water partition coefficients of ofloxacin, norfloxacin, lomefloxacin, ciprofloxacin, pefloxacin and pipemidic acid from 293.15 K to 323.15 K. The results show that 1-octanol/water partition coefficient of each quinolone increased with the increase of temperature. Based on the fluid phase equilibrium theory, the thermodynamic relationship of 1-octanol/water partition coefficient depending on the temperature was proposed, and the changes of enthalpy, entropy, and Gibbs free energy for quinolones partitioning in 1-octanol/water were determined, respectively. Quinolones molecules partitioning in 1-octanol/water was mainly an entropy driving process, during which the order degree of system decreased. The temperature effects of 1-octanol/water partition coefficient were investigated. The results show that its magnitude is the same as the values in the literature.
