Total synthesis and development of bioactive natural products

The first total synthesis and development of a variety of bioactive natural products have been accomplished by using carbohydrates as a chiral source. In addition, practically useful intermediates have been created, analogs of natural products have been prepared, their structure-activity relationships studied, and the large-scale preparations of medicinally useful compounds established. The key target molecules have been the "Big Four" antibiotics (macrolides, aminoglycosides, beta-lactams and tetracyclines), pyranonaphthoquinone antibiotics, glycosidase inhibitors, and a side-chain of cephem antibiotics.     

傅里叶变换红外光谱与拉曼光谱分析碳青霉烯药物亚胺培南的结构特征

本文采用傅里叶变换红外光谱和激光拉曼光谱对碳青霉烯药物亚胺培南进行光谱检测,并对其的分子振动光谱与结构特征进行分析和探讨,分析了亚胺培南在固相状态下的结构形式,从而为药物合成及质量控制提供了重要的参考价值。     

新药硫酸头孢匹罗的NMR研究

应用1D NMR、2D NMR （COSY、HMQC、HMBC、NOESY）及脉冲梯度场2D NMR技术[gHSQC（¹H-¹⁵N）、gHMBC（¹H-¹⁵N）]深入研究了第四代新型超广谱头孢菌素类抗生素硫酸头孢匹罗的结构,并首次对其¹H NMR、¹³C NMR谱和¹⁵N NMR谱的信号进行了全归属,通过NOESY实验对其立体结构提供有力依据.     

Tandem shock waves to enhance genetic transformation of Aspergillus niger

Filamentous fungi are used in several industries and in academia to produce antibiotics, metabolites, proteins and pharmaceutical compounds. The development of valuable strains usually requires the insertion of recombinant deoxyribonucleic acid; however, the protocols to transfer DNA to fungal cells are highly inefficient. Recently, underwater shock waves were successfully used to genetically transform filamentous fungi. The purpose of this research was to demonstrate that the efficiency of transformation can be improved significantly by enhancing acoustic cavitation using tandem (dual-pulse) shock waves. Results revealed that tandem pressure pulses, generated at a delay of 300 μs, increased the transformation efficiency of Aspergillus niger up to 84% in comparison with conventional (single-pulse) shock waves. This methodology may also be useful to obtain new strains required in basic research and biotechnology.     

Determination of the concentration of cephalosporin antibiotics in blood by infrared spectroscopy

We studied IR spectra of blood and cephalosporin antibiotics that are widely used in medical practice. We established the spectral regions that are suitable for determining their concentration in blood. It is shown using the antibiotic cephtriacson as an example that the IR spectroscopy method allows one to determine the concentrations of antibiotics in blood in the range of practical medical interest. We examined the possible transfer of antibiotics by blood erythrocytes. __________ Translated from Zhurnal Prikladnoi Spektroskopii, Vol. 74, No. 4, pp. 512–515, July–August, 2007.     

莽草酸途径中26种代谢物的NMR谱归属

莽草酸代谢途径广泛存在于植物、微生物与某些寄生虫中,是芳香氨基酸、植物激素与多种重要活性次生代谢物的主要合成通路.这些代谢物的系统核磁共振（NMR）研究尚不完备,且5-羟基吲哚乙酸与吲哚乳酸等代谢物的NMR数据归属尚不完整.本文对莽草酸代谢途径介导的26种代谢物（包括2种非芳香羧酸、2种植物激素、3种芳香类氨基酸、19种植物次生代谢物）结构进行了较为系统的NMR分析,对这些代谢物的¹H和¹³C NMR信号进行了归属,为植物化学及代谢组学研究提供了基础数据.     

Ultrasound in synthesis: natural products and supersonic reactions?

Sonochemical syntheses of a number of useful reagents such as samarium diiodide, sodium phenylselenide, tertiary alkoxides and the reducing agent [(PPh₃P)CuH]₆ are discussed. The rates of these sonochemical reactions can be increased by the addition of electron-transfer agents, such as benzophenone ketyls. These results would not be expected on the basis of mechanical effects alone and lend support to proposals that ultrasound acts preferentially on single electron-transfer processes. Ultrasound also allows the rapid and efficient generation of tetracarbonyliron, which can be trapped by simple organic compounds, such as conjugated dienes, vinyl epoxides and allylic alcohols. In the latter cases, this allows the facile preparation of π-allyltricarbonyliron lactone and lactam complexes that can be converted to give a range of biologically active β-, γ- and δ-lactones, including a number of alkaloids and antibiotics. In addition, the δ-lactone products have been incorporated into several complex multi-step syntheses of macrocyclic natural products. The synthesis of key fragments of the potent antiparasitic agent avermectin B1a demonstrates that the sonochemical reaction conditions are fully compatible with the synthesis of highly functionalized molecules.     

应用银溶胶膜探测水中抗生素的表面增强拉曼光谱研究

以自组装法制备的银溶胶膜为表面增强拉曼散射活性基底实现了对水中抗生素的痕量检测。采用微波加热法制备银溶胶,自组装法制备银溶胶膜。通过改变银溶胶的pH值及镀膜的次数,研究其对抗生素增强效果的影响。实验发现,采用不同pH值的银溶胶镀膜所获得的银溶胶膜的增强效果有很大差异,当银溶胶pH=4,且镀膜次数为五次时,增强效果最佳。以此银溶胶膜为基底对三种抗生素(氯霉素、环丙沙星、恩诺沙星)进行了SERS检测,可以检测到的最低浓度分别为120,15,120 nmol·L-1。结果表明,利用改进方法制备的银溶胶膜,可以对水中抗生素进行痕量检测,为实现养殖水中残留抗生素的检测提供了方法。     

Mechanisms of Ceftazidime and Ciprofloxacin Transport through Porins in Multidrug-Resistance Developed by Extended-Spectrum Beta-Lactamase <Emphasis Type="Italic">E.coli</Emphasis> Strains

Resistance towards antibiotics stands out today as a major issue in the clinical act of treatment of bacterial-generated infections. This process was characterized in proteoliposomes reconstituted from an E.coli strain isolated from invasive infections (blood culture) occurred in patients with a cardio-vascular device admitted for surgery. Fluorescence spectroscopy and patch-clamp technique have been used. Two types of antibiotics have been targeted: ceftazidime and ciprofloxacin. Antibiotics addition in proteoliposomes suspension undergoes a quenching in tryptophan residues from outer membrane porins structure, probably due to the formation of a transient non-fluorescent porin-antibiotic complex. Patch-clamp recordings revealed strong ion current blockages for both antibiotics, reflecting antibiotic–channel interactions but with varying strength of interaction. The present study puts forward the mechanism of multidrug-resistance in extended-spectrum beta-lactamase E.coli strains, as being caused by alterations of the antibiotics transport across the porins of the outer bacterial membrane.     

主要抗生素的太赫兹光谱检测与分析研究进展

抗生素具有治疗各种细菌感染或致病微生物感染类疾病的作用,获得主要抗生素的吸收特性可对抗生素添加进行有效的定性定量监测和控制,在医药、畜牧和水产业等领域都有重要意义和使用价值。太赫兹光谱技术作为一种无损、高效、便捷的新型光谱探测技术,在国防安全、信息通信、材料、环境生物医学、农业和食品安全等领域有良好的应用前景。文章介绍了太赫兹时域光谱技术(THz-TDS)检测系统的组成结构和工作原理,综述了现阶段太赫兹时域光谱技术在常用抗生素方面检测与分析的主要研究进展,重点归纳了β-内酞胺类、氨基糖苷类、四环素类、喹诺酮类、大环内脂类和磺胺类等主要抗生素的太赫兹定性识别与定量分析研究,给出了太赫兹时域光谱技术在主要抗生素检测方面的研究潜力和存在问题,为太赫兹技术未来用于主要抗生素定性定量快速检测仪器设备研发提供参考。     

共振瑞利散射法在抗生素类药物分析中的研究进展

对近6年来共振瑞利散射法在抗生素类药物分析中的研究与应用做了简要综述,主要从反应体系,线性范围,检出限等方面对几大类药物的研究现状进行了介绍。     

Surface‐enhanced Raman spectroscopy coupled with dendritic silver nanosubstrate for detection of restricted antibiotics

Surface‐enhanced Raman spectroscopy (SERS) coupled with dendritic silver nanosubstrates was used in this study for rapid detection and characterization of restricted antibiotics. Dendritic silver nanosubstrates were prepared through a simple replacement reaction and stored in deionized water for months. SERS methods with near‐IR excitation at 785 nm using silver nanosubstrates were evaluated for detection of three restricted antibiotics (i.e. enrofloxacin, ciprofloxacin, and chloramphenicol) prepared in standard solutions. SERS was capable of identifying and characterizing three antibiotics quickly and accurately. Silver dendrites exhibit satisfactory and consistent performance with an analytical enhancement factor of ∼10⁴. The limit of detection and limit of quantification for antibiotics could reach the level of 20 ppb. Silver dendrites can be kept in deionized water for up to 6 months with no signs of degradation in SERS performance. These results demonstrate a great potential of using SERS coupled with silver dendrites for rapid detection, classification, and quantification of chemical contaminants. Copyright © 2009 John Wiley & Sons, Ltd.     

Enzymatic Decomposition of Chitosan-Based Film Materials Modified by Antibiotics of the Cephalosporin Series

The enzymatic decomposition of film materials based on chitosan with inclusions of cephalosporin antibiotics on a substrate impregnated with Ringer–Locke’s solution was studied. The introduction of antibiotics led to a decrease in the rate of the enzymatic decomposition of chitosan, as in the case of chitosan lysis in the presence of aminoglycoside antibiotics. A possible reason for the decrease in the rate of the enzymatic decomposition of chitosan is suppression of polyelectrolyte swelling in the presence of low-molecular electrolytes including medicinal agents. The introduction of drugs in the chitosan-based film is a potential method for selectively decreasing the rate of enzymatic hydrolysis of chitosan for increasing the service life of the film material on a wound surface.     

基于紫外LED阵列光催化降解抗生素的研究

抗生素的大量使用对生态环境造成巨大的影响,光催化技术具有操作简单且无二次污染等特点被广泛应用于污染物的降解。在光催化降解抗生素过程中,光源对其降解效率至关重要,与传统的汞灯催化光源相比,紫外LED技术具有更高的能源效率及更低的功耗,使光催化工艺发生了巨大的变化。首先建立基于紫外LED阵列的光催化平台,采用光栅光谱仪和紫外照度计对LED阵列光源光谱特性及装置内光场分布进行测量分析。结果显示紫外LED光源波长介于265～295 nm之间,其主波长为275 nm,由于光场叠加效果,光照强度随着装置径向位置距离的增大而明显增大,装置轴向位置光照强度分布较为均匀;其次通过三维超景深显微镜、UV-Vis光谱测量技术对P25型光催化剂的粒子结构进行表征分析,同时使用半导体求导公式对TiO₂粉末进行禁带分析,结果显示TiO₂为球形,由于空气中相对湿度过大,水在TiO₂微粒表面的润湿性加强了微粒间的粘附力,因此有团聚现象产生,其禁带宽度为3.1 eV;最后以紫外LED阵列和高压汞灯为催化光源,P25型TiO₂为催化剂分别对甲基橙、磺胺类抗生素进行光催化降解,使用紫外-可见光分光光度计测量降解过程中的吸收光谱曲线,进而对抗生素降解率进行分析。结果表明,甲基橙和磺胺二甲嘧啶在紫外LED阵列为光源条件下均能够被降解,分别经过160和240 min的催化降解过程后,降解率分别达到70%和36%,符合一级动力学方程,经计算LED阵列光源与汞灯对甲基橙的降解动力学常数分别为-0.007 5和-0.113 5 min-1,对磺胺二甲嘧啶的降解动力学常数分别为-0.001 9和-0.019 4 min-1。因此对甲基橙和磺胺二甲嘧啶进行降解时,汞灯降解速率高于紫外LED阵列;由于紫外LED阵列和汞灯系统在催化降解污染物过程中功率和其与反应器中轴线距离不同,对两种光源的抗生素降解效率建立评价方法,即对紫外LED和汞灯以单位功率为标准进行距离降解效率分析,对于甲基橙,汞灯在单位功率下的距离降解效率高于紫外LED,但对于抗生素,紫外LED阵列的距离降解效率明显高于汞灯。依据以上各类光谱分析和应用结果,紫外LED阵列是一种有竞争力的光催化应用替代光源,此技术的广泛应用为抗生素的降解提供新途径。     

Supramolecular Conformational Effect in Complexations of Pectin and Chitosan Polysaccharides with Some Cephalosporin and Aminoglycoside Antibiotics

The reactions of the polysaccharides pectin (Pc) and chitosan (CTS) with antibiotics of cephalosporin and aminoglycoside series were studied. The complexation between the drugs and polymers was found to occur via hydrogen bonding. Dilution of the chitosan polycation increased the probability of occurrence of the negative ions of the cephalosporin antibiotic near the chain and lowered the probability of occurrence of the positive ions of aminoglycoside antibiotics, which affected the amount of adducts. When the pectin polyanion was diluted, the opposite situation was observed.     

A kinetic Monte Carlo approach to investigate antibiotic translocation through bacterial porins

Many relevant biological processes take place on time scales not reachable by standard all-atom computer simulations. The translocation of antibiotics through non-specific bacterial porins is an example. Microscopic effects compete to determine penetration routes and, consequently, free energy barriers to be overcome. Since bacteria can develop resistance to treatment also by reducing their antibiotic permeability, to understand the microscopic aspects of antibiotic translocation is an important step to rationalize drug design. Here, to investigate the translocation we propose a complete numerical model that combines the diffusion-controlled rate theory and a kinetic Monte Carlo scheme based on both experimental data and microscopically well-founded all-atom simulations. Within our model, an antibiotic translocating through an hour-glass-shaped channel can be described as a molecule moving on a potential of mean force featuring several affinity sites and a high central barrier. The implications of our results for the characterization of antibiotic translocation at in vivo concentrations are discussed. The presence of an affinity site close to the mouth of the channel seems to favor the translocation of antibiotics, the affinity site acting as a particle reservoir. Possible connections between results and the appearance of mutations in clinical strains are also outlined.     

Synergistic bactericidal effects and mechanisms of low intensity ultrasound and antibiotics against bacteria: a review

Low intensity ultrasonic therapy is always an important research area of ultrasonic medicine. This review concentrates on low intensity ultrasound enhancing bactericidal action of antibiotics against bacteria in vitro and in vivo, including planktonic bacteria, bacterial biofilms, Chlamydia, and bacteria in implants. These literatures show that low intensity ultrasound alone is not effective in killing bacteria, while the combination of low intensity ultrasound and antibiotics is promising. Low intensity ultrasound facilitating antibiotic treatment is still in its infancy, and still requires a great deal of research in order to develop the technology on medical treatment scale.     

Interaction of Moxifloxacin with Bovine Hemoglobin and Effect of the Coexistent Drugs on the Reaction

The interaction between moxifloxacin (MXFX) and Bovine Hemoglobin (BHb) was investigated at different temperatures by fluorescence spectroscopy. Results showed that the quenching mechanism of MXFX on BHb was a static quenching process with Förester spectroscopy energy transfer. The primary binding for MXFX was located at β-37 Tryptophan residue in hydrophobic cavity of BHb. Besides, weak negative cooperativity was found in drug's binding with BHb. Synchronous spectra revealed that the microenvironment and the conformation of serum albumin were changed during the reaction. Most antibiotics had no effect on the system of BHb-MXFX, except quinolone antibiotics. The system had good stability.     

Antifungal activity of multifunctional Fe3O4-Ag nanocolloids

In recent years, rapid increase has been observed in the population of microbes that are resistant to conventionally used antibiotics. Antifungal drug therapy is no exception and now resistance to many of the antifungal agents in use has emerged. Therefore, there is an inevitable and urgent medical need for antibiotics with novel antimicrobial mechanisms. Aspergillus glaucus is the potential cause of fatal brain infections and hypersensitivity pneumonitis in immunocompromised patients and leads to death despite aggressive multidrug antifungal therapy. In the present article, we describe the antifungal activity of multifunctional core-shell Fe₃O₄-Ag nanocolloids against A. glaucus isolates. Controlled experiments are also carried out with Ag nanocolloids in order to understand the role of core (Fe₃O₄) in the antifungal action. The minimum inhibitory concentration (MIC) of nanocolloids is determined by the micro-dilution method. MIC of A. glaucus is 2000 μg/mL. The result is quite promising and requires further investigations in order to develop a treatment methodology against this death causing fungus in immunocompromised patients.     

Image fusion through local feature extraction by using multi-scale top-hat by reconstruction operators

The purpose of image fusion is to combine useful image features of different original images into the final fusion image, which will produce one useful result image for different applications. One of the main difficulties of image fusion is extracting useful image features of different original images. In some cases, useful image features are local image features of the whole image. To efficiently extract local image features and produce an efficient fusion result, an image fusion algorithm based on the extracted local image features by using multi-scale top-hat by reconstruction operators is proposed in this paper. Firstly, multi-scale local feature extraction using multi-scale top-hat by reconstruction operators is discussed. Then, based on the extracted multi-scale local features of different original images, the useful image features for image fusion are constructed. Finally, the constructed useful image features for image fusion are combined into the final fusion image. Experimental results on different types of images show that, the proposed algorithm performs well for image fusion.