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Twelve new heteroleptic nickel(II) and copper(II) complexes of the type [M(L1–6)(Pfx)2] ( 1 – 12 ), where L1–6=2-benzylidenehydrazinecarbothioamide (L1), 2-benzylidene-N-methylhydrazinecarbothioamide (L2), 2-benzylidene-N-phenylhydrazinecarbothioamide (L3), 2-(4-methylbenzylidene)hydrazinecarbothioamide (L4), 2-(4-methylbenzylidene)-N-methylhydrazinecarbothioamide (L5) and 2-(4-methylbenzylidene)-N-phenylhydrazinecarbothioamide (L6), Pfx=pefloxacin and M=Ni(II) or Cu(II) have been synthesised, and their structures were confirmed by different spectral techniques. The spectral data and density functional theory (DFT) calculations supported the bonding of pefloxacin drug molecule via one of the carboxylate oxygen atoms and the pyridone oxygen atom, and the thiosemicarbazone ligand via the imine nitrogen and the thione sulfur atoms with the metal(II) ion, forming distorted octahedral geometry. In vitro antiproliferative activity of the synthesized complexes was evaluated against three human breast cancer (T47D, estrogen negative (MDA-MB-231) and estrogen positive (MCF-7)) as well as non-tumorigenic human breast epithelial (MCF-10a) cell lines, which showed the higher activity for the copper(II) complexes. The interaction of the synthesized complexes with an oncogenic protein H-ras (121 p) was explored by in silico molecular docking studies. Further, in silico pharmacokinetics and ADMET parameters were also analysed to predict the drug-likeness as well as non-toxic and non-carcinogenic behavior, and safe oral administration of the complexes.  相似文献   
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For the first time, we used multilocus sequence typing (MLST) to understand how Romanian group B streptococcus (GBS) strains fit into the global GBS population structure. Colonising isolates recovered from adult human females were tested for antibiotic resistance, were molecularly serotyped based on the capsular polysaccharide synthesis (cps) gene cluster and further characterised using a set of molecular markers (surface protein genes, pilus-encoded islands and mobile genetic elements inserted in the scpB-lmb intergenic region). Pulsed-field gel electrophoresis was used to complement the MLST clonal distribution pattern of selected strains. Among the 55 strains assigned to six cps types (Ia, Ib, II-V), 18 sequence types (STs) were identified by MLST. Five STs represented new entries to the MLST database. The prevalent STs were ST-1, ST-17, ST-19 and ST-28. Twenty molecular marker profiles were identified. The most common profiles (rib+GBSi1+PI-1, rib+GBSi1+PI-1, PI-2b and alp2/3+PI-1, PI-2a) were associated with the cps III/ST-17 and cps V/ST-1 strains. A cluster of fluoroquinolone-resistant strains was detected among the cps V/ST-19 members; these strains shared alp1 and IS1548 and carried PI-1, PI-2a or both. Our results support the usefulness of implementing an integrated genotyping system at the reference laboratory level to obtain the reliable data required to make comparisons between countries.  相似文献   
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The in vitro antibacterial activity of sitafloxacin using clinical isolates of Vibrio cholerae O1 was compared to other fluoroquinolones: ciprofloxacin, ofloxacin, sparfloxacin and levofloxacin. Against fluoroquinolone-resistant O1 strains, sitafloxacin was 4- to 16-fold more effective than other fluoroquinolones at MIC(90*). Against fluoroquinolone-susceptible O1 strains, the MIC(90) of sitafloxacin was 2- to 4-fold lower than other fluoroquinolones. This suggests sitafloxacin can be used in the treatment of infections caused by V. cholerae O1 strains including the fluoroquinolone-resistant strains.  相似文献   
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Fluoroquinolones (FQ) are antibiotics widely used in clinical practise, but the development of bacterial resistance to these drugs is currently a critical public health problem. In this context, ternary copper complexes of FQ (CuFQPhen) have been studied as a potential alternative. In this study, we compared the passive diffusion across the lipid bilayer of one of the most used FQ, ciprofloxacin (Cpx), and its ternary copper complex, CuCpxPhen, that has shown previous promising results regarding antibacterial activity and membrane partition. A combination of spectroscopic studies and molecular dynamics simulations were used and two different model membranes tested: one composed of anionic phospholipids, and the other composed of zwitterionic phospholipids. The obtained results showed a significantly higher membrane permeabilization activity, larger partition, and a more favourable free energy landscape for the permeation of CuCpxPhen across the membrane, when compared to Cpx. Furthermore, the computational results indicated a more favourable translocation of CuCpxPhen across the anionic membrane, when compared to the zwitterionic one, suggesting a higher specificity towards the former. These findings are important to decipher the influx mechanism of CuFQPhen in bacterial cells, which is crucial for the ultimate use of CuFQPhen complexes as an alternative to FQ to tackle multidrug-resistant bacteria.  相似文献   
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Aims: This study was carried out to find the prevalence of various plasmid‐mediated quinolone‐resistant (PMQR) determinants among the quinolone‐resistant clinical isolates of Shigella sp. from paediatric patients in Andaman & Nicobar Islands. Methods and Results: A total of 106 quinolone‐resistant Shigella isolates obtained from paediatric patients during hospital‐based surveillance from January 2003 to June 2010 were screened for the presence of various PMQR determinants. Of 106 isolates, 8 (7·5%) showed the presence of aac (6′)‐Ib‐cr and 3 (2·8%) harboured the qnrB genes with 2 (1·9%) of these isolates showing the presence of both. All the 9 isolates had uniform mutations in gyrA (S83L) and in parC (S80I). Conclusions: The prevalence of fluoroquinolone‐acetylating aminoglycoside acetyltransferase {aac (6′)‐Ib‐cr} gene is higher than qnrB gene among the clinical Shigella isolates. These PMQR determinants were detected in the Shigella isolates obtained from 2008–2010, indicating that it happens in a stepwise manner following the multiple mutations in quinolone resistance‐determining regions increase or extend resistance to quinolones or fluoroquinolones. Significance and Impact of Study: The prevalence of these genes are of grave concern as it may be horizontally transferred to other human pathogenic bacteria and can lead to therapeutic failure as a consequence of antimicrobial resistance, not only for the islands but also for the entire south‐east region. The results obtained should encourage further studies on the implications of the presence, distribution, association and variation of these determinants in our quest for understanding PMQR.  相似文献   
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High quinolone resistance rates were observed among oxyiminocephalosporin-resistant enterobacteria. In the present study, we searched for the prevalence of plasmid-mediated quinolone resistance (PMQR) genes within the 55 oxyiminocephalosporin-resistant enterobacteria collected in a previous survey. The main PMQR determinants were aac(6'')-Ib-cr and qnrB, which had prevalence rates of 42.4% and 33.3%, respectively. The aac(6'')-Ib-cr gene was more frequently found in CTX-M-15-producing isolates, while qnrB was homogeneously distributed among all CTX-M producers.  相似文献   
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