Interaction Between Gatifloxacin and Bovine Serum Albumin

Aim To study the reaction mechanism between gatifloxacin and bovine serumalbumin (BSA) at different pHs. Methods Fluorescence spectra and UV absorbance spectra were used.Results The binding constants were determined from a double reciprocal Lineweaver-Burk curves atdifferent pHs. The binding distance r under normal physiological condition was obtained according toFoster theory of non-radiative energy transfer. The binding force between gatifloxacin and BSA wasinferred by thermody-namical coordination. Conclusion The interaction between gatifloxacin and BSAseems to be strong and the main binding force is electrostatic force.

Gatifloxacin-铕荧光探针测定DNA

在pH 7.0±0.1的Tris-HCl缓冲溶液中,Eu3+与加替沙星形成的络合物受270 nm紫外光激发发出Eu3+的特征荧光峰,加入脱氧核糖核酸(DNA)能大大增强体系的荧光强度,由此建立GFLX-Eu3+络合物探针测定核酸的方法。与GFLX-Eu3+二元络合物相比,GFLX-Eu3+-DNA三元体系荧光强度显著增强,且最大吸收波长紫移5 nm,表明形成三元络合物。研究了反应的最佳条件,并初步探讨了GFLX-Eu3+络合物探针和DNA结合机制。

氟喹诺酮类抗菌剂Gatifloxacin

喹诺酮类抗菌剂对革兰阳性和阴性菌均有较强药效,被广泛用于治疗各种细菌感染。但目前临床使用的喹诺酮类药物常具有光毒性,并对胚胎和婴幼儿的生长发育有一定不良影响。Ｇａｔｉｆｌｏｘａｃｉｎ虽然也是氟喹诺酮类抗菌药,但其具有光毒性较小的特点,而且因其对细菌的拓扑...

Preparative Resolution of Gatifloxacin Enantiomers with Pre-Column Esterification Strategy and Comparing Their Enantioselectivity to Bacteria and Antibody

Gatifloxacin （GFX） is a kind of chiral fluoroquinolones compound due to the methyl group at the C-3 position of the piperazine ring[1]. Although the enantiomers of GFX show similar levels of antimicrobial activity and pharmacokinetics[2], the other biological activities （i.e., toxicity or enantioselective recognition to various receptors in vivo） of GFX enantiomers have not yet been studied. With this in mind, we developed a rapid and cost-effective high performance liquid chromatographic （HPLC） separation procedure for GFX enantiomers with a pre-column esterification strategy.

Potential Antimicrobial Effects of Gatifloxacin on Periodontopathic Bacteria in Vitro

The aim of this study was to identify the potential antibacterial effects of gatifloxacin on periodontal pathogens including Aggregatibacter actinomycetemcomitans, Porphyromonas gingi-valis, and Prevotella intermedia. The minimum inhibitory concentrations (MIC) of gatifloxacin and its bactericidal effects were investigated. Gatifloxacin inhibited the growth of all three kinds of periodontopathic bacteria tested in broth. The MIC value of 2.5 nM was found to be the most effective in inhibiting A. actinomycetemcomitans. An adenosine triphosphate biolumi-nescence assay revealed that gatifloxacin exhibited bactericidal effects on the tested bacteria in a time-dependent manner. The safety of gatifloxacin in mammalian cells was evaluated by assessing the viability of normal human dermal fibroblast (NHDF) cells treated with gatifloxacin. Almost all NHDF cells survived after 2-d culture, while 81% of the cells survived after 4-d culture when treated with 1.0 × 103 nM gatifloxacin. These results indicate that gatifloxacin is a possible drug for local administration to prevent periodontal infection.

Gatifloxacin inducing apoptosis of stromal fibroblasts through cross-talk between caspase-dependent extrinsic and intrinsic pathways

AIM: To reveal the cytotoxicity and related mechanisms of gatifloxacin(GFX) to stromal fibroblasts(SFs) in vitro.METHODS: SFs were treated with GFX at different concentrations(0.009375%-0.3%), and their viability was detected by MTT method. The cell morphology was observed using light/transmission electron microscope. The plasma membrane permeability was measured by AO/EB double-staining. Then cell cycle, phosphatidylserine(PS) externalization, and mitochondrial transmembrane potential(MTP) were analyzed by flow cytometry. DNA damage was analyzed by electrophoresis and immunostaining. ELISA was used to evaluate the caspase-3/-8/-9 activation. Finally, Western blotting was applied for detecting the expressions of apoptosis-related proteins.RESULTS: Morphological changes and reduced viability of GFX-treated SFs demonstrated that GFX above 0.009375% had cytotoxicity to SFs with dependence of concentration and time. GFX-treating cells also showed G1 phase arrest, increased membrane permeability, PS externalization and DNA damage, which indicated that GFX induced apoptosis of SFs. Additionally, GFX could activate the caspase-8, caspase-9, and caspase-3, induce MTP disruption, downregulate B-cell leukemia-2(Bcl-2) and B-cell leukemiaXL(Bcl-XL), and upregulate Bcl-2 assaciated X protein(Bax), Bcl-2-associated death promoter(Bad), Bcl-2 interacting domain(Bid) and cytoplasmic cytochrome C in SFs, suggesting that caspase-dependent extrinsic and intrinsic pathways were related to GFX-contributed apoptosis of SFs.CONCLUSION: The cytotoxicity of GFX induces apoptosis of SFs through triggering the caspase-dependent extrinsic and intrinsic pathways.

A NOVEL MOLECULARLY IMPRINTED POLYMER:SYNTHESIS AND ADSORPTION BEHAVIOR OF GATIFLOXACIN

A kind of molecularly imprinted polymer (MIPs) with high selectivity was prepared using methacrylic acid (MAA) as functional monomer, ethylene glycol dimethacrylate (EDMA) as crosslinker and Gatifloxacin as template. The effect of various parameters such as volume of solvent, functional monomer dosage, crosslinker dosage and polymerization time were investigated. The selective binding experiment for substrates show that the affinity and selectivity for Gatifloxacin were higher than that for blank polymer. Scatchard analysis show that the MIPs recognized template with two kinds of binding sites. The dissociation constant Kd and maximum adsorption quantity Qmax of these two kinds of binding sites were calculated: Kd1 and Qmax1 of the binding sites with high affinity were 8.67×10-4 mol/L and 28.19μmol/g, while Kd2 and Qmax2 of the binding sites with low affinity were1.05×10-3 mol/L and 33.20μmol/g respectively.

表面gatifloxacin和环丙沙星、阿米卡星和克拉霉素对于实验性治疗 chelonae海龟属分支杆菌角膜炎的效果比较

目的：在动物模型上测定局部gatifloxacin和环丙沙星、阿米卡星和克拉霉素对于治疗海龟属分支杆菌chelonae角膜炎的效果。

加替沙星拉曼光谱、紫外吸收光谱及微观结构的理论研究

基于密度泛函理论(Density functional theory,DFT),M06-2X/6-311G(d,p)基组水平下对加替沙星分子的初始结构进行优化.计算其振动频率,采用VEDA4软件基于势能分布(Potential energy distribution,PED)计算结果对特征振动模式进行了归属指认,并和实验光谱进行了对比.绘制了分子表面静电势,分析分子可能发生亲电和亲核反应的位点.利用含时密度泛函理论(Time-dependent density functional theory,TDDFT)计算了加替沙星分子的激发态,讨论了加替沙星分子内的电子跃迁.该研究为分析加替沙星的光谱和电子结构提供了理论基础.

A novel gatifloxacin-loaded intraocular lens for prophylaxis of postoperative endophthalmitis

Postoperative endophthalmitis(POE)has been the most threatening complication after cataract surgery,which perhaps can be solved by the antibiotic-loaded intraocular lens(IOL).However,most drug-loaded IOLs demonstrate insufficient drug quantity,short release time,increased implantation-related difficulties or other noticeable drawbacks.To prevent POE and to address these deficiencies,a drug-loaded copolymer IOL,prepared from poly(urethane acrylate)prepolymer,isobornyl methacrylate(IBOMA),N-vinyl-2-pyrrolidone(NVP),Irgacure 819,RUVA-93,and gatifloxacin(GAT),was rapidly fabricated via photocuring and by using a 3D-printed mold.This composite displayed an outstanding and controllable GAT release behavior in vitro,a high light transmittance,and a moderate refractive index.Also,it demonstrated improved strain stress and elongation compared with the reference commercial acrylic IOL material.In vivo tests demonstrated satisfying released drug concentration at the early treatment stage.In vitro and in vivo studies further confirmed the remarkable bacterial inhibition and prevention of POE by the proposed IOL,which also displayed good biocompatibility.These findings suggested that the GAT-loaded IOL could be a promising implant to prevent and cure POE,also the proposed methods could inspire more designs for various medical applications.

Determination of drug concentration in aqueous humor of cataract patients administered gatifloxacin ophthalmic gel

Background Ophthalmic gel has been developed to increase the drug concentration in aqueous humor and to retard the loss of drug from the conjunctival sac.The research was to compare the drug concentration in aqueous humor of cataract patients administered 0.3% gatifloxacin ophthalmic gel with that in patients administered 0.3% gatifloxacin ophthalmic solution.Methods Ninety-six patients with cataract （96 eyes） were randomly assigned to 8 groups.The patients in groups 1-4received topical gatifloxacin 0.3% ophthalmic gel and those in groups 5-8 received gatifloxacin 0.3% ophthalmic solution.The dose regimen was 1 drop, 4 times a day for 3 consecutive days prior to cataract surgery.On the day of surgery, 1drop was applied at 15, 30, 60 or 120 minutes before commencement of cataract surgery in groups 1 and 5, groups 2 and 6, goups 3 and 7, and groups 4 and 8, respectively.Aqueous humor was extracted during the cataract surgery for the analysis of gatifloxacin concentration..Results The concentrations of gatifloxacin in aqueous humor were （0.24±0.25） μg/ml, （1.11±0.74） μg/ml, （2.32±2.01）μg/ml and （1.85±1.14） μg/ml in groups 1 to 4, and （0.16±0.25） μg/ml, （0.31±0.24） μg/ml, （0.75±0.28） μg/ml and （0.33±0.22） μg/ml in groups 5 to 8, respectively.Patients receiving gatifloxacin ophthalmic gel showed greater mean values of gatifloxacin concentration in aqueous humor than those receiving gatifloxacin solution, and such differences were significant with P 〈0.05 for all comparisons except that between groups 1 and 5.Conclusion Topical gatifloxacin ophthalmic gel can attain significantly greater drug concentrations in human aqueous humor than gatifloxacin ophthalmic solution.

Pulse radiolysis study on gatifloxacin——A fluoroquinolone antibiotic

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.

Development of an electrochemical immunoassay for detection of gatifloxacin in swine urine

To detect gatifloxacin （GAT） residue in swine urine, an electrochemical immunoassay was established, An indirect competitive immunoassay was developed, in which the coating antigen is immobilized in an enzyme-linked immunosorbent assay （ELISA） plate and GAT residue from the sample competes with the limited binding sites in added anti-GAT antibody. Horseradish peroxidase （HRP） conjugated to goat anti-rabbit IgG was used as the enzymatic label. A carbon fiber working electrode was constructed and current signals were detected by using hydrogen peroxide as a substrate and hydroquinone as an electrochemical mediator. The electrochemical immunoassay was evaluated by analysis of GAT in buffer or swine urine and an average value of half inhibition concentration （IC50） of 8.9 ng/ml was obtained. Excellent specificity of the antibody was achieved with little cross-reaction with Iomefloxacin （3.0%）, ciprofloxacin （3.0%）, and ofloxacin （1.9%） among commonly used （fluoro）quinolones. In conclusion, the im- munoassay system developed in this research can be used as a rapid, powerful and on-site analytical tool to detect GAT residue in foods and food products.

Studies on Interaction between Gatifloxacin and Bovine Serum Albumin by Spectroscopy

The interaction of gatifloxacin （HGA） with bovine serum albumin （BSA） at 15 and 37 ℃ has been investigated by fluorescence quenching spectroscopy in aqueous solution. The bimolecular quenching rate constant was determined by Stem-Volmer curves and the values were Kq=9.28× 10^12 L·mol^-1·s^-1 （15 ℃） and Kq=8.51 ×10^12 L·mol^-1·s^-1 （37 ~C）. The results showed that the fluorescence quenching mechanism of BSA by HGA was a static quenching procedure. The thermodynamic parameters indicated that electrostatic forces played major role in the interaction of BSA with HGA. Studies on the relationship between the concentration of HGA and the fluorescence intensity of BSA showed that BSA and HGA bound at the molar ratio 1 ： 1 and the equilibrium constant K0 was 6.80 ×10^4 L·mol^-1. The binding distances between BSA and HGA and the energy transfer efficiency were obtained based on the Ftrster＇s theory.

Distribution and Transfer of Gatifloxacin Between Two Microemulsion Phases with Different Structures in SDS/n-C5H11 OH/H2O System

At a weight ratio of n-C5H11OH/H2O=50/50, when the total content of sodium dodecyl sulfate （SDS） was less than 6.0%, the ternary mixture of SDS/n-C5H11OH/H2O coexisted in two immiscible microemulsions. The distribution and transfer of gatifloxacin （GTFX） between the two phases were studied using UV-Vis and electrochemistry AC impedance spectra. The results show that GTFX transferred from the upper phase （W/O） to the lower phase （O/W or bicontinuous microemulsion）, but a small amount of SDS transferred from the lower phase to the upper phase correspondingly with the increase of the total SDS content at a total GTFX concentration of 1.0×10^-5 mol/L. The addition of GTFX did not change the structures of the two different phases fundamentally, but resulted in the transfer and redistribution of GTFX and SDS, so the electric properties of the system were changed correspondingly.

Synthesis, Characterization and Activity against Staphylococcus of Metal（Ⅱ）-Gatifloxacin Complexes

Three novel isostructural complexes M（gatx）2（H2O）2·4H2O [gatx=gatifloxacin, M = Zn （1）, Ni （2） and Co （3）] were synthesized at room temperature and structurally characterized by elemental analysis, IR and single crystal X-ray diffraction, which exhibit a similar mononuclear structure, in which the metal ion is coordinated by two gatifloxacin and two aqua ligands to furnish a distorted octahedral geometry, and show different activities against staphylococcus due to the different metal ions in the structures.

A Selective and Sensitive Fluorescence Probe for Se（IV） Based on Fluorescence Quenching of Gatifloxacin

A novel high selective and sensitive fluorescence probe termed gatifloxacin was discovered based on fluorescence ＂on-off＂ phenomenon in the presence of Se（IV）. In the Tris-HCl/acetonitrile（3：7, volume ratio, Tris-HCl 0.05 mol/L, pH=7.3） system, the fluorescence intensity of gatifloxacin was linearly decreased with the concentration increase of Se（IV） in a range of 1.0×10-5--5.0×10-5 mol/L with a correlation coefficient of 0.9979（R2=0.9958） and in a range of 5.0×10-5--1.0 ×10-4 mol/L with a correlation coefficient of 0.9973（R2=0.9946）. The detection limit of Se（IV） was 1.70×10-6mol/L.

Photodegradation of fluoroquinolone antibiotic gatifloxacin in aqueous solutions

Fluoroquinolone antibiotics (FQs) are frequently detected as emerging pollutants in aqueous environments.In this study,kinetics,influencing factors and mechanisms on the photodegradation of gatifloxacin,a representative FQ,were investigated.The photodegradation follows the pseudo-first-order kinetics.Gatifloxacin photodegrades with a quantum yield of (5.94 ± 0.95) × 10 3 in pure water and undergoes direct photolysis as well as self-sensitized photodegradation.The FQ photodegrades slower in freshwater and seawater than in pure water,which is attributed to the integrative effects of pH and the aqueous dissolved matter (e.g.,humic acids and NO 3-) on the photodegradation.A toxicity test using Vibrio fischeri revealed the formation of hazardous photoproducts.