Fungal transformation of dydrogesterone and inhibitory effect of its metabolites on the respiratory burst in human neutrophils

The biotransformation of the synthetic hormone dydrogesterone (1) by a number of fungal strains - including Cephalosporium aphidicola, Rhizopus stolonifer, Cunninghamella elegans, and Fusarium lini - afforded ten different metabolites, compounds 2-11. From a structural point of view, these transformations involved a combination of hydroxylation, oxidation, reduction, and/or epoxidation. The pregnane-based metabolites 10 and 11 are new compounds. All the known compounds were obtained for the first time from 1 by fungal transformation. The metabolites 3, 5, and 8 showed more-potent respiratory-burst inhibitory activity than the substrate 1 in a neutrophil-based cellular assay (Table 3).     

Two new alkaloids from Pachysandra terminalis and their antibacterial activity assessment

Phytochemical investigation of a 90 % ethanol extract of Pachysandra terminalis Sieb. Et Zucc led to the isolation of a novel alkaloid, terminamine T (1); a new pregnane-type alkaloid, terminamine U (2); and four known pregnane-type alkaloids (3-6). The structures of these compounds were elucidated on the basis of nuclear magnetic resonance spectra, mass spectrometry data, single-crystal X-ray diffraction, and by a comparison with data from the literature. All compounds were evaluated for their antibacterial activities against gram-positive (S. aureus, ATCC 29213) and gram-negative (E. coli, ATCC 25922) bacteria. Compounds 2-6 exhibited generally modest to poor antibiotic properties. Furthermore, compound 2 showed antibacterial activity against methicillin-resistant Staphylococcus epidermidis (MRSE), methicillin-resistant Staphylococcus aureus (MRSA), and methicillin-resistant Staphylococcus aureus USA300 (LAC) with a minimal inhibitory concentration (MIC) value of 32 μg/mL (75 μM) and minimum bactericidal concentration (MBC) values of 64, 128, and 128 μg/mL (150, 300, and 300 μM), respectively.     

一株海洋真菌Aspergillus jensenii LW128的次级代谢产物及其抗菌活性研究

【目的】研究一株西北太平洋深海沉积物来源真菌Aspergillus jensenii LW128的次级代谢产物及其抗菌活性。【方法】利用硅胶柱色谱(silica gel column chromatography)、凝胶柱色谱(Sephadex LH-20 column chromatography)和反相高效液相色谱(reversed-phase high-performance liquid chromatography, RP-HPLC)等方法对菌株的发酵粗提物进行分离纯化得到单体化合物;将核磁共振波谱(nuclear magnetic resonance, NMR)、质谱(mass spectrometry, MS)数据与相关文献报道数据进行比对后确定化合物结构;采用肉汤微量稀释法测定化合物的抗菌活性。【结果】从海洋真菌Aspergillus jensenii LW128中分离并鉴定了10个已知化合物,分别为diorcinol D(1)、diorcinol K(2)、diorcinol I(3)、(+)-(7S)-7-O-methylsydonic acid (4)、(+)-s...     

Two new metabolites from Portulaca oleracea and their anti-inflammatory activities

Two new metabolites, identified as 6-phenylbenzofuran-4-ol, named olerabenzofuran (1), and 2-(furan-2-yl)− 6-hydroxy-1 H-inden-1-one, named oleraindenone (2), together with eight furan compounds obtained for the first time, (+)-pinoresinol (3), (-)-syringaresinol (4), (+)-diasyringaresinol (5), (+)-episyringaresinol (6), (2 S)− 1-[2-(furan-2-yl)− 2-oxoethyl]− 5-oxopyrrolidine-2-carboxylic acid (7), methyl (2 S)− 1[2-(furan-2-yl)− 2-oxoethyl]− 5-oxopyrrolidine-2-carboxylate (8), drynaran (9), and 2-furoic acid (10), were isolated from Portulaca oleracea L., and spectroscopic methods, including 1D and ²D NMR and UHPLC-ESI-QTOF/MS spectrometry techniques, were employed to determine their structures. It was suggested that both olerabenzofuran (1) and oleraindenone (2) could significantly inhibit inflammatory factor interleukin-1β (IL-1β) in RAW 264.7 cells induced by LPS.     

Synthesis and antibacterial activity of new long-chain-alkyl bile acid-based amphiphiles

The efficient synthesis of some bile acid-derived cationic amphiphiles with a flexible long hydrocarbon tail was investigated. Firstly, the modification on the side-chain carboxyl of bile acids was carried out efficiently by one-pot amidation of bile acids and a long-chain aliphatic amine in the presence of HOBt and DCC to introduce a flexible long hydrocarbon tail. Then the hydrophilic concave side of bile acids with hydroxyl groups was further modified into cationic groups for strengthening hydrophilicity. This strategy offered a very straightforward and efficient method for access to the designed amphiphiles in good overall yields. The preliminary results showed that an increase both in the length of the hydrophobic tail and in the number of charged groups resulted in a decrease in the CMC of bile acid-derived cationic amphiphiles. And the bile acid-derived cationic amphiphiles with a flexible longer hydrocarbon tail and more positive charges had the highest antibacterial and antimicrobial activity.     

Co-culture of Aspergillus sydowii and Bacillus subtilis induces the production of antibacterial metabolites

The co-culture strategy, which mimics natural ecology by constructing an artificial microbial community, is a useful tool to activate the biosynthetic gene clusters to generate new compounds. However, without optimization of fermentation conditions, the antagonism between the microbes often interferes with the production of secondary metabolites. In this study, the fermentation conditions of co-culture of Aspergillus sydowii and Bacillus subtilis were optimized by response surface methodology to increase the production of active metabolites against Staphylococcus aureus. After optimization, the inhibitory rate of the co-culture extract was 74.62%, which was 29.20% higher than that of the initial conditions. Meanwhile, a total of 15 newly biosynthesized metabolites were detected only in optimized co-culture, occupying 13.2% of all detected metabolites. The structures of the 12 metabolites with high variable importance in projection score were elucidated by the established LC-MS/MS approach integrated with various metabonomic tools. Among them, 7 metabolites were newly induced and the content of other 5 metabolites increased by 1.1–2.4 folds in optimized co-culture. The bioassay of metabolites in co-culture against S. aureus indicated that compounds (?)- (7S)- 10-hydroxysydonic acid, serine sydonate and macrolactin U’ contributed much to the increment of antibacterial activity. This study demonstrated that optimizing the fermentation conditions of co-culture was beneficial to changing the metabolite profile and effective to induce the biosynthesis of active metabolites.     

Synthesis,antiproliferative and antibacterial activity of new amides of salinomycin

A series of 11 novel amides of salinomycin were synthesized for the first time. All the obtained compounds were found to show potent antiproliferative activity against human cancer cell lines including the drug-resistant cancer cells. Four new salinomycin derivatives revealed good antibacterial activity against clinical isolates of methicillin-resistant Staphylococcus epidermidis (MRSE).     

Pyranones from kiwi-associated fungus Fusarium tricinctum and their antibacterial activity

Four new pyrone derivatives, fusaritricins A–D (1−4), together with five known analogues, were obtained from the kiwi endophytic fungus Fusarium tricinctum. Their structures were established by extensive spectroscopic data analysis and their absolute configurations were determined by quantum chemical calculations. Compounds 1, 2, 3, and 9 exhibited antibacterial activity against plant pathogen Pseudomonas syringae pv. Actinidiae (Psa) with MIC values of 128, 128, 64, and 64 µg/mL, respectively. This is the first report of anti-Psa activity of pyrone derivatives.     

Preparation and antibacterial activity of chitosan nanoparticles

Chitosan nanoparticles, such as those prepared in this study, may exhibit potential antibacterial activity as their unique character. The purpose of this study was to evaluate the in vitro antibacterial activity of chitosan nanoparticles and copper-loaded nanoparticles against various microorganisms. Chitosan nanoparticles were prepared based on the ionic gelation of chitosan with tripolyphosphate anions. Copper ions were adsorbed onto the chitosan nanoparticles mainly by ion-exchange resins and surface chelation to form copper-loaded nanoparticles. The physicochemical properties of the nanoparticles were determined by size and zeta potential analysis, atomic force microscopy (AFM), FTIR analysis, and XRD pattern. The antibacterial activity of chitosan nanoparticles and copper-loaded nanoparticles against E. coli, S. choleraesuis, S. typhimurium, and S. aureus was evaluated by calculation of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Results show that chitosan nanoparticles and copper-loaded nanoparticles could inhibit the growth of various bacteria tested. Their MIC values were less than 0.25 microg/mL, and the MBC values of nanoparticles reached 1 microg/mL. AFM revealed that the exposure of S. choleraesuis to the chitosan nanoparticles led to the disruption of cell membranes and the leakage of cytoplasm.     

康美肤烧伤膏抗菌活性

目的观察康美肤烧伤膏的抗菌作用。方法采用试管稀释法测定康美肤烧伤膏对常见致病菌的最低抑菌浓度(M IC)及对大鼠Ⅱ度烧烫伤创面接种金黄色葡萄球菌的实验治疗模型创面菌落计数的影响。结果康美肤烧伤膏对常见致病菌的M IC范围在3.90~62.50 g/L。结论康美肤烧伤膏具有较强的抗菌活性和较广的抗菌谱。     

一株类芽孢杆菌的分离鉴定及其抗革兰氏阴性菌活性测定

【背景】随着碳青霉烯类和多粘菌素类可转移耐药基因的发现及扩散,多重耐药革兰氏阴性细菌感染更加难以治疗。【目的】筛选有效拮抗革兰氏阴性菌的菌株,为新型抗生素的发掘奠定基础。【方法】利用胰蛋白胨大豆琼脂培养基筛选土壤源细菌,通过16S rRNA基因序列鉴定其种属;通过全基因组测序,antiSMASH比对分析菌株产抗生素潜能,双层琼脂平板法验证其抗菌活性;通过甲醇萃取其次级代谢产物,高效液相色谱串联质谱(HPLC-MS/MS)进行次级代谢产物分析。【结果】从北京周边土壤样品中分离到一株类芽孢杆菌CAU136 (Paenibacillus pabuli CAU136),经过生物信息学分析和antiSMASH比对,表明该菌株有较强合成次级代谢产物的潜能,双层琼脂平板法验证其能抑制多株革兰氏阴性菌生长,HPLC-MS/MS检测结果显示其可能分泌多粘菌素E。【结论】类芽孢杆菌CAU136可能分泌多粘菌素E,能有效拮抗革兰氏阴性菌。     

A new diterpene from the fungal mycelia of Hericium erinaceus

One new diterpene (1) and new compound (2), along with four known compounds (3–6) were isolated from the fungal mycelia of Hericium erinaceus by the tracking method of antibacterial activity. The structures of compounds (1–6) were elucidated on the basis of spectral data. Compound (3) showed strong antibacterial activity against Helicobacter pylori (ATCC43504) and compounds (1), (2) and (4) showed moderate antibacterial activity. Compound (1) exhibited good cytotoxicity against three human cancer cell lines (K562, LANCAP, HEP2).     

Lipase-catalyzed synthesis and antibacterial activity of N-vanillylnonanamide

N-vanillylnonanamide (VAN) was successfully synthesized from vanillylamine hydrochloride by enzymatic catalysis in supercritical carbon dioxide (SC–CO₂). Five commercial lipases, Novozyme 435, Lipozyme IM, Amano PS, Amano G and Sigma Candida cylindracea type VII, as biocatalysts for VAN synthesis were compared. Lipozyme IM exhibited best yields of tested lipases. Various parameters such as time, temperature, pressure and vanillylamine hydrochloride/nonanoic anhydride ratio that influenced the reaction were investigated. Nonanoic anhydride showed the best acyl donor of the employed substrates. An amidation yield of 40% was obtained when nonanoic anhydride and Lipozyme IM were used at 170 bar and 50 °C for 23 h in SC–CO₂. Besides, addition of 2 mM divalent salts (CuCl₂ and ZnCl₂) significantly increased 11–23% yield of the VAN. The enzyme operational stability suggested that Lipozyme IM maintained over 50 °C of the initial activity for the synthesis of VAN after reuse for 69 h. Furthermore, in vitro, VAN behaved as a potential antibacterial against Escherichia coli.     

猪源产细菌素芽孢杆菌的筛选及抑菌特性

【背景】抗生素作为生长促进剂在畜牧业中的滥用,出现了严重的耐药基因富集和扩散问题,发掘新兴的生长促进剂作为饲料添加剂市场潜力巨大,目前益生菌制剂的开发最具潜力。【目的】通过对散养健康育肥猪粪便中芽孢杆菌的分离筛选,获得对典型肠道病原菌具有显著抑菌活性的芽孢杆菌,确定其产生的细菌素特性,以此对芽孢杆菌作为猪养殖业生长促进剂的潜力进行评价。【方法】采用梯度稀释涂平板法分离可培养细菌,利用牛津杯法检测菌株的抑菌活性。通过微生物形态及16S r RNA基因序列分析,确认6株产细菌素菌株的分类地位,并对其抗生素耐药性、细菌素稳定性及生理生化特征进行比较分析。【结果】从116株纯培养物中筛选得到6株对指示病原细菌具有显著抑菌效应的产细菌素芽孢杆菌,其中2株为贝莱斯芽孢杆菌(Bacillus velezensis),3株为枯草芽孢杆菌(Bacillus subtilis),1株为地衣芽孢杆菌(Bacillus licheniformis)。菌株B.licheniformis DY7和B.subtilis FX4对致泻、产肠毒素、出血性Escherichia coli均有显著的抑制效果,对头孢噻肟和红霉素高度敏感,其细菌素在p H 3.0-9.0、50-100°C水浴处理后仍具有明显的抑菌活性。【结论】猪源产细菌素芽孢杆菌DY7和FX4具有高效的病原细菌抑菌能力,所产细菌素稳定性较好,具有作为动物生长促进剂的应用潜力。     

Biosynthesis and antibacterial activity of ZnO nanoparticles using Trifolium pratense flower extract

Zinc oxide (ZnO) has broad applications in various areas. Nanoparticle synthesis using plants is an alternative to conventional physical and chemical methods. It is known that the biological synthesis of nanoparticles is gaining importance due to its simplicity, eco-friendliness and extensive antimicrobial activity. Also, in this study we report the synthesis of ZnO nanoparticles using Trifolium pratense flower extract. The prepared ZnO nanoparticles have been characterized by UV–Vis absorption spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM) with Energy dispersive X-ray analysis (EDX). Besides, this study determines the antimicrobial efficacy of the synthesized ZnO nanoparticles against clinical and standard strains of S. aureus and P. aeruginosa and standard strain of E. coli.     

Chemistry and biological activity of azoprenylated secondary metabolites

N-Prenyl secondary metabolites (isopentenylazo-, geranylazo-, farnesylazo- and their biosynthetic derivatives) represent a family of extremely rare natural products. Only in recent years have these alkaloids been recognized as interesting and valuable biologically active secondary metabolites. To date about 35 alkaloids have been isolated from plants mainly belonging to the Rutaceae family, and from fungi, bacteria, and/or obtained by chemical synthesis. These metabolites comprise anthranilic acid derivatives, diazepinones, and indole, and xanthine alkaloids. Many of the isolated prenylazo secondary metabolites and their semisynthetic derivatives are shown to exert valuable in vitro and in vivo anti-cancer, anti-inflammatory, anti-bacterial, anti-viral, and anti-fungal effects. The aim of this comprehensive review is to examine the different types of prenylazo natural products from a chemical, phytochemical and biological perspective.     

Synthesis and antibacterial activity of novel ketolides with 11,12-quinoylalkyl side chains

A series of quinoylalkyl side chains was designed and synthesized, followed by introduction into ketolides by coupling with building block 6 or 32. The corresponding targets 7a–n, 33b, and 33e were tested for their in vitro activities against a series of macrolide-sensitive and macrolide-resistant pathogens. Some of them showed a similar antibacterial spectrum and comparable activity to telithromycin. Among them, two C2-F ketolides, compounds 33b and 33e, displayed excellent activities against macrolide-sensitive and macrolide-resistant pathogens.     

Chemical composition,antibacterial and antifungal activities of flowerhead and root essential oils of Santolina chamaecyparissus L., growing wild in Tunisia

The antimicrobial properties of essential oil from various Santolina species have not been investigated enough in the previous studies dealing with the biological activities of medicinal plants. In Tunisia, Santolina chamaecyparissus L. (Asteraceae) is the only Santolina species recorded and is used as vermifuge and emmenagogue. The chemical composition, antibacterial and antifungal properties of essential oils from the flowerheads and roots of spontaneous S. chamaecyparissus growing in Tunisia and the chemical composition which leads to the Tunisian chemotype are investigated here for the first time. Essential oils isolated by hydro distillation from flowerheads and roots of S. chamaecyparissus were analyzed by GC and GC/MS. Two methods served for antimicrobial assays of the essential oils: diffusion in a solid medium and micro-well dilution assay. Antifungal tests were carried out by the agar incorporation method. Sixty-seven constituents were identified from the essential oil of the flowerhead. The major constituents were: 1,8-cineole and β-eudesmol. Two non identified compounds were present at the highest concentration in root oil. Flowerhead oil was characterized by high contents in monoterpenes and sesquiterpenes oxygenated compounds. The flowerhead essential oil demonstrated potent of antibacterial properties against Pseudomonas aeruginosa ATCC and Enterococcus faecalis ATCC, with MIC of 0.625 μg/ml. These findings demonstrate that the flowerhead essential oils of S. chamaecyparissus have excellent antibacterial properties and for this reason they could contribute to decrease the problem of microbial resistance to antibiotics.