纳米银在细菌纤维素凝胶膜中的原位合成及性能表征

在细菌纤维素纳米纤维网络结构中采用吐伦试剂与含醛基化合物原位反应生成纳米银颗粒, 制备了纳米银/细菌纤维素(n-Ag/BC)复合凝胶膜, 研究了不同反应条件对复合材料的银含量、 化学结构和晶体结构的影响以及n-Ag/BC的微观结构和纳米银在纤维素网络中的存在形态; 探讨了纳米银颗粒在纤维素网络中的形成机理; 采用伤口常见细菌之一金黄色葡萄球菌测试了n-Ag/BC的抑菌性能; 将n-Ag/BC与胎鼠表皮细胞共培养考察了材料的生物相容性. 研究结果表明, 在细菌纤维素纳米网络结构中可生成直径约为几十纳米的单质纳米银粒子; n-Ag/BC的银含量随着吐伦试剂浓度的增加而增加, 同时银含量还取决于含醛基化合物的用量; 原位反应生成纳米银粒子后细菌纤维素的晶型和结晶度没有发生变化; 纳米银颗粒在细菌纤维素纳米网络结构的交叉处生成, 复合材料n-Ag/BC对金黄色葡萄球菌的抑菌率达到99%以上, 不影响细胞的增殖和分化过程, 具有良好的生物相容性, 是一种有广阔应用前景的创伤修复抗感染材料.     

Influence of Open Chain and Cyclic Structure of Peptidomimetics on Antibacterial Activity in E. coli Strains

An efficient method for the synthesis of functionalized peptidomimetics via multicomponent Ugi reaction has been developed. The application of trifluoroethanol (TFE) as a reaction medium provided desired products with good yields. Further, using the developed cyclisation reaction, the obtained peptidomimetics were transformed into the cyclic analogues (diketopiperazines, DKPs). The goal of the performed studies was to revised and compare whether the structure of the obtained structurally flexible acyclic peptidomimetics and their rigid cycling analogue DKPs affect antimicrobial activity. We studied the potential of synthesized peptidomimetics, both cyclic and acyclic, as antimicrobial drugs on model E. coli bacteria strains (k12, R2–R4). The biological assays reveal that DKPs hold more potential as antimicrobial drugs compared to open chain Ugi peptidomimetics. We believe that it can be due to the rigid cyclic structure of DKPs which promotes the membrane penetration in the cell of studied pathogens. The obtained data clearly indicate the high antibiotic potential of synthesized diketopiperazine derivatives over tested antibiotics.     

A new eco-friendly strategy for the synthesis of novel antimicrobial spiro-oxindole derivatives via supramolecular catalysis

Novel spiro-oxindole derivatives were synthesised by one-pot multicomponent reaction using isatins, urea and 1,3-dicarbonyls. β-Cyclodextrin, an oligosaccharide, catalysed the reaction and can be reused for further reaction after recovery. This developed synthetic route is environmentally benign in which water is used as solvent to produce excellent yields of products. The synthesised compounds were evaluated for their antimicrobial activities against two bacteria and two fungi. All the synthesised spiro-oxindoles exhibit significant antimicrobial activity.     

Green one-pot synthesis of N -bisphosphonates as antimicrobial and antioxidant agents

A straightforward and greener approach has been developed for the synthesis of novel aminomethylene bisphosphonates by one-pot reaction of diverse aryl/heteroaryl amines with dialkyl phosphite and triethyl orthoformate using CuO nanoparticles as catalyst under microwave irradiation and solvent-free conditions. This is an ecofriendly synthetic approach for swift access to a library of diverse aminomethylene bisphosphonates. All the synthesized new compounds were evaluated for their antimicrobial activity by disc diffusion method and antioxidant activity by DPPH, H2O2, and NO methods. The title compounds exhibited significant antioxidant and considerable antimicrobial activities.     

微米级花状结构铜/聚乙烯吡咯烷酮的制备及其抗菌性能

采用液相还原的方法,以聚乙烯吡咯烷酮(PVP)为修饰剂,氯化铜为前驱体,水合肼为还原剂,成功制备了微米级Cu/PVP花状结构.采用扫描电子显微镜和X射线粉末衍射仪分析了所得样品的形貌与结构;利用差热分析测定了样品的热稳定性,并采用肉汤稀释法测试了其抗菌性能.结果表明,所制备的样品具有由多个Cu/PVP圆片组装而成的直径为6μm的花状结构,其形貌依赖于反应条件.与此同时,花状结构的Cu/PVP对金黄色葡萄球菌和大肠杆菌具有明显的抗菌作用,相应的最小抑菌浓度(MIC)和最小杀菌浓度(MBC)分别为:41.25mg/L、82.5mg/L,以及20.63mg/L、82.5mg/L.与单一Cu纳米微粒相比,花状结构的Cu/PVP复合物的抗菌持久性明显较好.     

Synthesis,Antimicrobial Activity and Molecular Docking Study of Thiazole Derivatives

The reaction of 4‐thiochromane thiocarbohydrazone with a series of hydrazonoyl halides in dioxane in the presence of triethylamine afforded novel thiochromane derivatives incorporating 1,3‐thiazole moiety. The structure of the latter compounds was established by elemental analysis and spectral technique and by their chemical transformation. Moreover, the antimicrobial activity of the newly synthesized compounds was screened and the results showed that some compounds have higher activity than the applied fungicide and bactericide. The antimicrobial activity of the most active compounds was interpreted by molecular docking study.     

Synthesis of Novel 3-Substituted Pyridothienopyrimidine Derivatives with Biological Evaluation as Antimicrobial Agents

Novel 3-substituted pyridothienopyrimidine derivatives have been synthesized via the reaction of 2-{7,9-dimethyl-4-oxopyrido[3',2':4,5]thieno[3,2-d]pyrimidin-3(4H)-yl}acetohydrazide(5) with a variety of active reagents and chemicals. Structures of the newly synthesized compounds were established based on spectral data. The resulting pyridothienopyrimidine derivatives were evaluated for their possible antimicrobial activity and some of them represent a new class of potentially antimicrobial compounds, especially compounds 9 and 18 which displayed the highest activity against Gram-positive bacteria, Gram-negative bacteria, and Fungi in MIC range of 0.12-1.95 μg/mL.     

Antimicrobial activities of polymeric quaternary ammonium salts from poly(glycidyl methacrylate)s

Amino poly(glycerol methacrylate)s (PGOHMAs) were synthesized from linear and 8‐arm poly(glycidyl methacrylate)s (PGMAs) via ring opening reactions with methylethylamine (MEA), diethylamine, and dipropylamine, respectively, which were further modified by quaternization reaction using methyl iodide to obtain quaternized PGMAs (QPGMAs for short). The products were characterized by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance, gel permeation chromatography, and thermogravimetric analysis. The amination percentage of amino PGOHMAs and the degree of quaternization of QPGMAs were calculated by elemental analysis and X‐ray photoelectron spectroscopy, respectively. According to the solubility test results, 8‐arm PGOHMA modified with MEA (S8‐MEA) is the only water‐soluble derivative of amino PGOHMAs and was employed as a positive control for the comparison with QPGMAs. Antimicrobial studies on these PGMA derivatives were carried out by testing the minimum inhibitory concentration and the bacteria inhibitive rate against Escherichia coli and Staphylococcus aureus. The results indicated that QPGMAs possessed higher antimicrobial activity than S8‐MEA and exhibited increased antimicrobial activity against both bacteria with an increased degree of quaternization in weak basic conditions. Moreover, the chemical structure of PGMA derivatives and pH value of the assay conditions were found to affect the antimicrobial activity. Copyright © 2013 John Wiley & Sons, Ltd.     

Simultaneous Grafting Polymerization of Acrylic Acid and Silver Aggregates Formation by Direct Reduction Using γ Radiation onto Silicone Surface and Their Antimicrobial Activity and Biocompatibility

The modification of medical devices is an area that has attracted a lot of attention in recent years; particularly, those developments which search to modify existing devices to render them antimicrobial. Most of these modifications involve at least two stages (modification of the base material with a polymer graft and immobilization of an antimicrobial agent) which are both time-consuming and complicate synthetic procedures; therefore, as an improvement, this project sought to produce antimicrobial silicone (PDMS) in a single step. Using gamma radiation as both an energy source for polymerization initiation and as a source of reducing agents in solution, PDMS was simultaneously grafted with acrylic acid and ethylene glycol dimethacrylate (AAc:EGDMA) while producing antimicrobial silver nanoparticles (AgNPs) onto the surface of the material. To obtain reproducible materials, experimental variables such as the effect of the dose, the intensity of radiation, and the concentration of the silver salt were evaluated, finding the optimal reaction conditions to obtain materials with valuable properties. The characterization of the material was performed using electronic microscopy and spectroscopic techniques such as ¹³C-CPMAS-SS-NMR and FTIR. Finally, these materials demonstrated good antimicrobial activity against S. aureus while retaining good cell viabilities (above 90%) for fibroblasts BALB/3T3.     

Characterization of H3PO4/HNO3–NANO2 oxidized bacterial cellulose and its usage as a carrier for the controlled release of cephalexin

Biocompatibility, biodegradation, good sorption characteristics, and unique structure of highly oxidized bacterial cellulose (OBC) are of great interest for the development of new drug delivery systems. In this study, OBC with 9.6, 13.0 and 19.5% carboxyl groups for 5, 20, and 48 h of synthesis, respectively, was successfully obtained using the HNO₃/H₃PO₄–NaNO₂. The results of morphological analysis showed that with an increase in the number of carboxyl groups, OBC fibers become thicker and rougher. Fourier-transform infrared spectroscopy showed the formation of carboxyl groups in the OBC after the oxidation reaction. The crystallinity of the samples according to X-Ray diffraction analysis decreased with increasing reaction time. The immobilization of cephalexin in the polymer matrix was studied in detail, it took 120 min to achieve balance in the solution with a concentration of 1 mg/ml, and the maximum amount of a sorbed antibiotic reached 43 mg/g. The drug release in vitro at 37 °C in PBS with pH 7.4 and 2.0 was prolonged. Various models were used to describe the release mechanism, the best of which was Ritger-Peppas with a diffusion exponent value ranging from 0.743 to 0.830, which explains the drug release mainly through non-Fickian diffusional release. The cephalexin-loaded OBC showed high antimicrobial activity against Gram-negative bacteria Escherichia coli and Gram-positive bacteria Staphylococcus aureus. The structure and properties of the resulting highly oxidized cellulose make it an excellent candidate as a drug delivery carrier with prolonged antimicrobial drug release characteristics.

     

芳香基苯并咪唑衍生物的合成、表征及抑菌活性研究

在微波辐射下,通过二茂铁磺酰氯和相应的苯并咪唑合成了4种芳香基苯并咪唑衍生物。经^1H NMR、MS及元素分析确证产物结构。通过X线衍射测定了化合物4a的晶体结构。用琼脂稀释法测定化合物抑菌活性,并与对照药剂50%多菌灵可湿性粉剂比较,结果表明化合物4a～4d对番茄早疫病菌、烟草赤星病菌和小麦赤霉病菌有与对照药剂近似的抑菌活性。     

Synthesis and Antimicrobial Screening of Fused Heterocyclic Pyridines

In an attempt to find a new class of antimicrobial agents, a series of pyridoxazepine, pyridothiazepine, triazepine, naphthyridine, pyridopyrimidine, and other related products containing pyridine moiety were synthesized via the reaction of 2‐amino‐6‐chloro‐3,5‐dicyanopyridine 1 with nucleophilic chemical reagents. These compounds were screened for cytotoxicity and their antimicrobial activity. Most of products showed inhibitory effect.     

Synthesis,Characterization, and Pharmacological Evaluation of Some New Pteridine‐Based Heterocycles as Antimicrobial Agents

Considering pteridine as a worthy structure for improving probes of magnificent therapeutic potentials, some new pteridine conjugates were synthesized by aminomethylation of benzopteridinethione with a variety of primary aromatic amines and formaldehyde solution (37%) through the Mannich reaction. The proposed mechanism of formation of the synthesized compounds was discussed, and the structure of the newly synthesized compounds was elucidated on the basis of their IR, ¹H NMR, ¹³C NMR, mass spectral, and elemental analyses. Furthermore, some selected compounds were evaluated in vitro for their antimicrobial activities; the preliminary data stated that the majority of the tested compounds exhibited significant antimicrobial activity. Analogues 22 , 23 , 20 , 19 , 24 , and 15 were found to be the most potent against all the tested microorganisms.     

Tobramycin and Nebramine as Pseudo‐oligosaccharide Scaffolds for the Development of Antimicrobial Cationic Amphiphiles

Antimicrobial cationic amphiphiles derived from aminoglycoside pseudo‐oligosaccharide antibiotics interfere with the structure and function of bacterial membranes and offer a promising direction for the development of novel antibiotics. Herein, we report the design and synthesis of cationic amphiphiles derived from the pseudo‐trisaccharide aminoglycoside tobramycin and its pseudo‐disaccharide segment nebramine. Antimicrobial activity, membrane selectivity, mode of action, and structure–activity relationships were studied. Several cationic amphiphiles showed marked antimicrobial activity, and one amphiphilic nebramine derivative proved effective against all of the tested strains of bacteria; furthermore, against several of the tested strains, this compound was well over an order of magnitude more potent than the parent antibiotic tobramycin, the membrane‐targeting antimicrobial peptide mixture gramicidin D, and the cationic lipopeptide polymyxin B, which are in clinical use.     

Synthetic Studies towards the Calcium-Dependent Lipopeptide Antibiotic Cadaside B

In the current global crisis of antimicrobial resistance, antimicrobial peptides represent a promising source of alternative antibiotics. Recently discovered cadaside B, a novel calcium-dependent antibiotic, exhibits potent antimicrobial activity towards Gram-positive pathogens including multi-drug resistant strains. These properties, coupled with a novel structure, non-cytotoxicity, and low likelihood of developing resistance render cadaside B an important synthetic target. Herein, a synthetic strategy towards cadaside B is reported with the key steps involving on-resin depsipeptide bond formation and solution-phase macrolactamization. Good agreement of the synthetic cadaside B MS/MS fragmentation pattern was observed with the natural product, but a different ¹H NMR spectrum and absence of antimicrobial activity suggest an undetected epimerization event took place during the synthesis. Herein the findings of our synthetic journey and suggestions for future directions are presented.     

The cathelicidins--structure, function and evolution

The cathelicidin family of host defense peptides includes a group of cationic and usually amphipathic peptides that display a variety of activities related to host defense functions, among which the most acknowledged is a direct antimicrobial activity against various microbial pathogens. All members of this family are synthesized as precursors characterized by an N-terminal cathelin-like domain which is relatively well conserved also in evolutionary distant vertebrates. By contrast, the C-terminal region, which carries the active peptide, appears to be a focus for genetic mechanisms that have selectively generated a considerable sequence diversity. This process is particularly striking in Cetartiodactyls, where repeated gene duplication events and subsequent divergence have produced an array of distinct family members. The corresponding mature cathelicidin peptides are considerably diverse in length, amino acid sequence and structure, variously adopting alpha-helical, elongated or beta-hairpin conformations. The diverse nature of these peptides may account for distinct functions and for a diverse spectrum of activity and/or antimicrobial potency.     

Bacteria‐Assisted Activation of Antimicrobial Polypeptides by a Random‐Coil to Helix Transition

The application of antimicrobial peptides (AMPs) is largely hindered by their non‐specific toxicity against mammalian cells, which is usually associated with helical structure, hydrophobicity, and charge density. A random coil‐to‐helix transition mechanism has now been introduced into the design of AMPs, minimizing the toxicity against mammalian cells while maintaining high antimicrobial activity. By incorporating anionic phosphorylated tyrosine into the cationic polypeptide, the helical structure of AMPs was distorted owing to the side‐chain charge interaction. Together with the decreased charge density, the AMPs exhibited inhibited toxicity against mammalian cells. At the infectious site, the AMPs can be activated by bacterial phosphatase to restore the helical structure, thus contributing to strong membrane disruptive capability and potent antimicrobial activity. This bacteria‐activated system is an effective strategy to enhance the therapeutic selectivity of AMPs.     

Design and Synthesis of Novel C4‐Linked Substituted 2H‐Chromen‐2‐one‐hypoxanthine Hybrids as Potential Antimicrobial Agents: An Approach to Molecular Docking Studies

We present here design and synthesis of very efficient, high‐yielded and simple approach of a series of C₄‐linked coumarin–hypoxanthine pharmacophores 1 ( a–j ) with moderate to excellent in vitro antimicrobial activity. According to earlier studies, potential modification at C₄‐position of coumarin ring provided excellent bioactive molecules. All the titled compounds were characterized by spectroscopic and elemental analyses. Titled compounds have been developed via systematic tuning of coumarin ring substitutions, which are prepared from the well‐known Pechmann condensation reaction. The addition of a pendent nucleobase in hypoxanthine group improved the in vitro antimicrobial activity. Computational studies were also mimicking the potent biomolecules. A good pharmacokinetic profile is suggested by theoretical calculation of absorption, distribution, metabolism, and excretion properties. Therefore, synthesis of these titled compounds provided an insight towards better antimicrobial agents.     

3-间硝基苯基/对硝基苯基-6-芳基-1, 2, 4-三唑并[3, 4-b]-1, 3, 4-噻二唑衍 生物的合成

报道了以3-间硝基苯基/对硝基苯基-4-氨基-5-巯基-1,2,4-三唑与芳酸在磷酰氯的作用下,合成了16个标题化合物,并研究了合成反应的条件。观察了部分标题化合物对金黄色葡萄球菌和大肠杆菌有明显的抑菌作用。     

Comparison of antibacterial activity of natural and hydroformylated essential oil of Thymus capitatus growing wild in north Sardinia with commercial Thymus essential oils

Thymus capitatus growing wild in Sardinia showed different essential oil composition if grown surrounding Cagliari than in north Sardinia. Here we verify the composition and antimicrobial activity of the oil to make it suitable for the cosmetic and confectionery industries. With the aim of improving the scent and the antimicrobical activity of T. capitatus essential oil, a hydroformylation reaction was carried out to transform the unsaturated components of the oil into the corresponding aldehydes. The essential oil of T. capitatus exhibited a significant antibacterial activity (MIC 0.125-0.5 mg/mL), and was also found effective on C. albicans (MIC 0.125 mg/mL). After hydroformylation, several new irregular terpenoid aldehydes were detected. The perfume of the new terpenic-like aldehydes is very agreeable and, therefore, the acceptability of the aroma is remarkably improved, but the antimicrobial activity was not increased.