Synthesis of novel benzoxazocino quinoliniums and quinolones under PTC conditions and their application in Suzuki cross coupling reaction for the construction of polynuclear heteroaromatics

A general and highly efficient synthetic protocol under phase transfer catalytic condition has been established for the synthesis of fused tetracyclic oxazocinoquinolone analogues which served as the precursors for novel biaryl quinolones using microwave assisted Suzuki cross coupling reaction.     

UPLC-MS法同时测定牛奶中磺胺类、喹诺酮类、甾体激素类及四环素类兽药残留

建立并优化了同时测定牛奶中10种磺胺类、6种喹诺酮类、8种甾体激素类以及1种四环素类药物共25种兽药残留的超高效液相色谱-串联质谱检测方法。样品中目标药物经5%乙酸乙腈提取,HLB固相萃取小柱净化后,通过UPLC-MS测定,外标法定量。25种兽药在不同加标浓度下的回收率为61.6%~119.2%,组内相对标准偏差(RSD)为2.5%~13.4%,组间RSD为5.8%~14.2%,方法检出限为0.5~2.0μg/kg。     

巴洛沙星-Tb^3＋-ATP荧光体系的建立及其分析应用

在二元配合物巴洛沙星-Tb^3＋中加入ATP,Tb^3＋在其特征波长545nm处的荧光强度增强,据此建立了新的巴洛沙星Tb^3＋-ATP荧光体系。在最优化实验条件下,增强的荧光强度与ATP的浓度呈良好的线性关系,线性范围为2．0×10^-6-3．0×10^-5mol／L,检出限为8．0×10^-7mol／L。详细的机理研究表明,ATP能与巴洛沙星-Tb^3＋形成大的三元络合物荧光体系。新建立的荧光体系成功地应用于ATP注射液中ATP的定量检测。对不同批次ATP注射液进行加标回收试验,回收率为101％-106％,测定结果的相对标准偏差为1．1％-1．9％（n=5）。     

Design and Synthesis of (2-oxo-1,2-Dihydroquinolin-4-yl)-1,2,3-triazole Derivatives via Click Reaction: Potential Apoptotic Antiproliferative Agents

A mild and versatile method based on Cu-catalyzed [2+3] cycloaddition (Huisgen-Meldal-Sharpless reaction) was developed to tether 3,3’-((4-(prop-2-yn-1-yloxy)phenyl)methylene)bis(4-hydroxyquinolin-2(1H)-ones) with 4-azido-2-quinolones in good yields. This methodology allowed attaching three quinolone molecules via a triazole linker with the proposed mechanism. The products are interesting precursors for their anti-proliferative activity. Compound 8g was the most active one, achieving IC₅₀ = 1.2 ± 0.2 µM and 1.4 ± 0.2 µM against MCF-7 and Panc-1 cell lines, respectively. Moreover, cell cycle analysis of cells MCF-7 treated with 8g showed cell cycle arrest at the G2/M phase (supported by Caspase-3,8,9, Cytochrome C, BAX, and Bcl-2 studies). Additionally, significant pro-apoptotic activity is indicated by annexin V-FITC staining.     

Biological Effects of Quinolones: A Family of Broad-Spectrum Antimicrobial Agents

Broad antibacterial spectrum, high oral bioavailability and excellent tissue penetration combined with safety and few, yet rare, unwanted effects, have made the quinolones class of antimicrobials one of the most used in inpatients and outpatients. Initially discovered during the search for improved chloroquine-derivative molecules with increased anti-malarial activity, today the quinolones, intended as antimicrobials, comprehend four generations that progressively have been extending antimicrobial spectrum and clinical use. The quinolone class of antimicrobials exerts its antimicrobial actions through inhibiting DNA gyrase and Topoisomerase IV that in turn inhibits synthesis of DNA and RNA. Good distribution through different tissues and organs to treat Gram-positive and Gram-negative bacteria have made quinolones a good choice to treat disease in both humans and animals. The extensive use of quinolones, in both human health and in the veterinary field, has induced a rise of resistance and menace with leaving the quinolones family ineffective to treat infections. This review revises the evolution of quinolones structures, biological activity, and the clinical importance of this evolving family. Next, updated information regarding the mechanism of antimicrobial activity is revised. The veterinary use of quinolones in animal productions is also considered for its environmental role in spreading resistance. Finally, considerations for the use of quinolones in human and veterinary medicine are discussed.     

反相高效液相色谱／质谱法同时测定鸡肉中5种喹诺酮药物残留

采用反相高效液相色谱／四级杆串联质谱（RP-HPLC／MS／MS）同时测定鸡肉中的5种喹诺酮药物（quinolones，QNs）。均质后的鸡肉样品采用磷酸盐缓冲溶液和乙腈的混和溶液提取。提取液经正己烷液-液分配（LLP）去除脂肪后，用C18固相萃取（SPE）柱净化，氨化甲醇洗脱，洗脱液用氮气吹干，流动相定容后，分析物采用LC／MS／MS电喷雾电离（ESI），正离子，多反应监测（MRM）模式检测，外标法定量。在添加浓度2．5～10μg/kg范围内，5种QNs的回收率在79．8％～95．1％之间；相对标准偏差（RSD）均小于11．7％。环丙沙星、丹诺沙星、恩诺沙星检出限（LOD）为0．5μg／kg，沙托沙星为1．0μg／kg，氟甲喹为0．1μg／kg。     

QSAR study and VolSurf characterization of anti-HIV quinolone library

Antiviral quinolones are promising compounds in the search for new therapeutically effective agents for the treatment of AIDS. To rationalize the SAR for this new interesting class of anti-HIV derivatives, we performed a 3D-QSAR study on a library of 101 6-fluoro and 6-desfluoroquinolones, taken either from the literature or synthesized by us. The chemometric procedure involved a fully semiempirical minimization of the molecular structures by the AMSOL program, which takes into account the solvatation effect, and their 3D characterization by the VolSurf/GRID program. The QSAR analysis, based on PCA and PLS methods, shows the key structural features responsible for the antiviral activity.     

泡腾辅助液相微萃取/高效液相色谱法检测蜂蜜中7种喹诺酮类药物

以密度小于水且具有可切换亲水性的壬酸作为萃取剂,通过加入Na2CO3和H2SO4改变溶液pH值,使壬酸完成从疏水性到亲水性再到疏水性的转换,同时利用原位产生的CO2鼓泡加大接触面积,完成对分析物的萃取,建立了基于可切换亲水性溶剂的泡腾辅助液相微萃取（EA－LPME－SHS）/高效液相色谱－荧光检测法（HPLC－FLD）测定蜂蜜中7种喹诺酮类药物（QNs）的分析方法。最佳提取条件如下：萃取剂为200 μL壬酸;pH调节剂为400 μL 2.0 mol/L Na2CO3和300 μL 2.0 mol/L H2SO4;提取时间为1.5 min。结果表明,5种喹诺酮类药物在2.0～200 μg/L范围内呈良好线性（诺氟沙星和环丙沙星为2.0～100 μg/L）,相关系数（r2）为0.999 5～0.999 9;在10、100、500 ng/g加标水平下,7种待测药物的回收率为62.8%～117%,日内（n = 3）和日间（n = 6）相对标准偏差（RSD）不大于6.2%,检出限为3.0 ng/g,定量下限为10 ng/g。该方法的提取过程均在注射器内完成,无需离心即可实现相分离,具有绿色环保、操作简便、省时等特点。     

Structure of 1,4-dihydro-1-ethyl-4-iminecinnoline-3-carboxylic acids, classical isosters of quinolone antibacterials: Crystal structures of hydrochlorides of 7-chloro and 7-methyl derivatives

Crystal structures of hydrochlorides of 7-chloro- and 7-methyl-4-iminecinnoline analogs of antibacterial quinolones have been determined by X-ray diffraction methods. The cell parameters for the 7-chloro (1) analog in the space group P2₁/c are a = 9.061(1), b = 19.062(1), c = 7.310(1)Å, = 104.92(1)°, Z = 4, and D _calc = 1.569 g/cm³ and for the 7-methyl (2) analog in the space group P are a = 7.277(5), b = 9.080(5), c = 10.058(5) Å, = 106.10(1), = 102.38(1), = 90.18(1)°, Z = 2, and D _calc = 1.429 g/cm³. Despite geometrical equivalency of methyl and chlorine and some resemblance of their packings, the crystal structures are not isostructural. Each compound forms a strong intramolecular hydrogen bond between protonated 4-imine (a donor) and 3-carboxylic (an acceptor) groups. Compounds with a similar bond, but with reversed functionality and orientation of the 3-carboxylic group, form common quinolones, being mostly 4-oxoquinoline-3-carboxylic acids. The difference should exclude chemical affinity of 4-imine analogs to the guanine base of a bacterial DNA in DNA-gyrase complex, as proposed by Shen et al. ² for 4-oxoquinoline-3-carboxylic acids showing antibacterial activity. Also the free acidic function of a carboxyl group may significantly lower permeability of 4-imine-3-carboxylic analogs of quinolones. Surprisingly, they have demonstrated antibacterial activity comparable with that of nalidixic acid.