Thermal solvent-free synthesis of chromonyl chalcones, pyrazolines and their in vitro antibacterial, antifungal activities

A facile and ecofriendly synthesis of new chromonyl chalcones 3a-b from 3-formylchromone 1 and active methyl compounds 2a-b is reported under thermal solvent-free heating condition in good yields. The chromonyl chalcones 3a-b were used as intermediates under green condition for the synthesis of new bioactive pyrazoline derivatives 4a-f. The compounds were tested for antimicrobial activity by disk diffusion assay with slight modifications against Gram-positive, Gram-negative strains of bacteria as well as fungal strains. The investigation of antimicrobial screening revealed that compounds 3a-b and 4a-f showed antibacterial and antifungal activities.     

Extraction methods and bioautography for evaluation of medicinal plant antimicrobial activity

A comparative study on the antimicrobial properties of extracts from medicinal plants obtained by two different methods was carried out. The screening of the antimicrobial activity of extracts from six plants was conducted by a disc diffusion test against Gram-positive, -negative and fungal organisms. The most active extracts (inhibition diameter >/=12 mm) were assayed for the minimum inhibitory concentration and submitted to phytochemical screening by thin-layer chromatography and bioautography. The results obtained indicate that the diethyl ether extracts were the most efficient antimicrobial compounds. The activity was more pronounced against Gram-positive and fungal organisms than against Gram-negative bacteria. Bioautography showed that the antimicrobial activity was probably due to flavonoids and terpenes.     

Molecular properties prediction and synthesis of novel 1,3,4-oxadiazole analogues as potent antimicrobial and antitubercular agents

In the present investigation, a series of 1,5-dimethyl-2-phenyl-4-{[(5-aryl-1,3,4-oxadiazol-2-yl)methyl]amino}-1,2-dihydro-3H-pyrazol-3-one were subjected to molecular properties prediction, drug-likeness by Molinspiration (Molinspiration, 2008) and MolSoft (MolSoft, 2007) software, lipophilicity and solubility parameters using ALOGPS 2.1 program. The compounds followed the Lipinski ‘Rule of five’ were synthesized for antimicrobial and antitubercular screening as oral bioavailable drugs/leads. Maximum drug-likeness model score (0.95) was found for compound, 4a. All the synthesized compounds were characterized by IR, NMR and mass spectral analysis followed by antimicrobial and antimycobacterial screening. Among the title compounds, compound 4d showed pronounced activity against Mycobacterium tuberculosis H₃₇Rv and isoniazid resistant M. tuberculosis (INHR-TB) with minimum inhibitory concentrations (MICs) 0.78 μM and 1.52 μM, respectively. The compound, 4a showed maximum activity against all bacterial strains with MIC 4–8 μg/mL comparable to standard drug ciprofloxacin, while the compounds, 4e and 4k showed maximum antifungal activity with MIC 8–16 μg/mL less active than standard drug fluconazole.     

Synthesis and biological evaluation of some novel thiazole substituted benzotriazole derivatives

A series of novel hybrid molecules 4a-y containing thiazole and benzotriazole templates were designed and synthesized. The structures of the synthesized compounds were elucidated by IR, (1)H NMR, (13)C NMR and mass spectral data. All the synthesized compounds were tested for their antimicrobial activity (zone of inhibition) against Gram-positive, Gram-negative strains of bacteria as well as fungal strains. After that minimum inhibitory concentrations (MICs), minimum bactericidal concentrations (MBCs) and minimum fungicidal concentrations (MFCs) of all the synthesized compounds were determined. The investigation of antimicrobial screening data revealed that most of the tested compounds showed moderate to good microbial inhibitions.     

Thermal solvent-free synthesis of chromonyl chalcones,pyrazolines and their in vitro antibacterial,antifungal activities

A facile and ecofriendly synthesis of new chromonyl chalcones 3a-b from 3-formylchromone 1 and active methyl compounds 2a-b is reported under thermal solvent-free heating condition in good yields. The chromonyl chalcones 3a-b were used as intermediates under green condition for the synthesis of new bioactive pyrazoline derivatives 4a-f. The compounds were tested for antimicrobial activity by disk diffusion assay with slight modifications against Gram-positive, Gram-negative strains of bacteria as well as fungal strains. The investigation of antimicrobial screening revealed that compounds 3a-b and 4a-f showed antibacterial and antifungal activities.     

Antimicrobial screening and active compound isolation from marine bacterium NJ6-3-1 associated with the sponge <Emphasis Type="Italic">Hymeniacidon perleve</Emphasis>

Twenty-nine marine bacterial strains were isolated from the sponge Hymeniacidon perleve at Nanji island, and antimicrobial screening showed that eight strains inhibited the growth of terrestrial microorganisms. The strain NJ6-3-1 with wide antimicrobial spectrum was identified as Pseudoalteromonas piscicida based on its 16S rRNA sequence analysis. The major antimicrobial metabolite, isolated through bioassay-guide fractionation of TLC bioautography overlay assay, was identified as norharman (a beta-carboline alkaloid) by EI-MS and NMR.     

Screening of basidiomycetes for antimicrobial activities

As a part of a screening programme developed to evaluate the antimicrobial activity of basidiomycetes, 317 isolates representing 204 species collected in Spain were screened against a range of human clinical pathogens and laboratory controls. Extracts from 45% of the isolates, representing 109 species, showed antimicrobial activity. Antibacterial activity was more pronounced than antifungal activity. The proportion of extracts from basidiomycetes showing antimicrobial activity was similar to or above that obtained for representative orders of Ascomycetes, such as Pezizales and Xylariales, but lower than that produced by members of the orders Diaporthales, Eurotiales, Hypocreales, Leotiales and Sordariales. Suprageneric taxa (orders and families) did not show pronounced differences in their antimicrobial activities though such differences were observed at the genus level, suggesting that the ability to produce these bioactive compounds is not homogenously distributed amongst the basidiomycetes. Isolates from some species showed large differences in their ability to produce metabolites with antimicrobial activity, possibly reflecting genetic differences at the infraspecific level.     

Synthesis of thiazole-based substituted piperidinone oximes: Profiling of antioxidant and antimicrobial activity

The synthesis of novel thiazole-based piperidinone oximes and screening of their antioxidant and antimicrobial activity are described. The obtained results revealed that the electronic effects of active substituents at C-4 terminals of phenyl rings on either side of piperidinone skeleton, as well as at 2-hydrazinyl thiazole, played a major role in development of antioxidant and antimicrobial activity. Antioxidant activity seems to be based also on radical dissipating ability of the thiazole ring. The nucleophilic character of sulfur in thiazole and lipophilic nature of piperidinone skeleton substantially influenced the observed antimicrobial activity of thiazole-based piperidinone oximes. Among the synthesized compounds, 2,6-bis(4-hydroxy-3-methoxyphenyl)-1-methylpiperidin-4-one O-(2-(2-(4-hydroxy-3-methoxybenzylidene)hydrazinyl)thiazol-4-yl) oxime exhibited excellent antioxidant activity whereas compound 2,6-bis(4-chloro phenyl)-1-methylpiperidin-4-one O-(2-(2-(4-nitrobenzylidene)hydrazinyl)thiazol-4-yl)oxime emerged as an outstanding antimicrobial agent.     

Evaluation of antimicrobial activity of selected plant extracts by rapid XTT colorimetry and bacterial enumeration

The aim of this study was to screen and evaluate the antimicrobial activity of indigenous Jordanian plant extracts, dissolved in dimethylsulfoxide, using the rapid XTT assay and viable count methods. XTT rapid assay was used for the initial screening of antimicrobial activity for the plant extracts. Antimicrobial activity of potentially active plant extracts was further assessed using the "viable plate count" method. Four degrees of antimicrobial activity (high, moderate, weak and inactive) against Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa, respectively, were recorded. The plant extracts of Hypericum triquetrifolium, Ballota undulata, Ruta chalepensis, Ononis natrix, Paronychia argentea and Marrubium vulgare had shown promising antimicrobial activity. This study showed that while both XTT and viable count methods are comparable when estimating the overall antimicrobial activity of experimental substances, there is no strong linear correlation between the two methods.     

Investigation of the antimicrobial activity of soy peptides by developing a high throughput drug screening assay

BackgroundAntimicrobial resistance is a great concern in the medical community, as well as food industry. Soy peptides were tested against bacterial biofilms for their antimicrobial activity. A high throughput drug screening assay was developed using microfluidic technology, RAMAN spectroscopy, and optical microscopy for rapid screening of antimicrobials and rapid identification of pathogens.MethodsSynthesized PGTAVFK and IKAFKEATKVDKVVVLWTA soy peptides were tested against Pseudomonas aeruginosa and Listeria monocytogenes using a microdilution assay. Microfluidic technology in combination with Surface Enhanced RAMAN Spectroscopy (SERS) and optical microscopy was used for rapid screening of soy peptides, pathogen identification, and to visualize the impact of selected peptides.ResultsThe PGTAVFK peptide did not significantly affect P. aeruginosa, although it had an inhibitory effect on L. monocytogenes above a concentration of 625 µM. IKAFKEATKVDKVVVLWTA was effective against both P. aeruginosa and L. monocytogenes above a concentration of 37.2 µM. High throughput drug screening assays were able to reduce the screening and bacterial detection time to 4 h. SERS spectra was used to distinguish the two bacterial species.ConclusionsPGTAVFK and IKAFKEATKVDKVVVLWTA soy peptides showed antimicrobial activity against P. aeruginosa and L. monocytogenes. Development of high throughput assays could streamline the drug screening and bacterial detection process.General significanceThe results of this study show that the antimicrobial properties, biocompatibility, and biodegradability of soy peptides could possibly make them an alternative to the ineffective antimicrobials and antibiotics currently used in the food and medical fields. High throughput drug screening assays could help hasten pre-clinical trials in the medical field.     

银杏内生菌的分离及其抑菌活性筛选

从健康的银杏（Ginkgo biloba）茎和叶片中分离内生菌,结果从银杏叶和茎上共分离到内生真菌20株,其中9株来自银杏茎部,11株来自银杏叶部;内生放线菌23株,其中15株来自于银杏茎部,8株来自于银杏叶部;内生细菌15株,其中8株来自于银杏茎部,7株来自于银杏叶部。以金黄色葡萄球菌（Staphylococcus aureus）、枯草芽胞杆菌（Bacillus subtilis）、大肠埃希菌（Escherichia coli）、黑曲霉（Aspergillus niger）、酿酒酵母（Saccharomyces cerevisiae）作为指示菌,采用双层平板法对内生菌进行抑菌活性筛选,结果表明：20株内生真菌中有12株出现了抑菌活性,有抑菌活性菌株的比例为60.0%;23株内生放线菌中,仅3株出现了抑菌活性,有抑菌活性菌株的比例为13.0%;15株内生细菌中,有4株出现了抑菌活性,有抑菌活性菌株的比例为26.7%。     

Studies on heterocyclic compounds: spiro [indole-3,2'-thiazolidine] derivatives. Antimicrobial activity of monohalogenated 3'-phenylspiro 3H-indole-3,2'-thiazolidine-2,4' (1H)-diones

The following halogenated 3'-phenyl [3H-indole-3,2'-thiazolidine]-2,4'(1H)-dione of general formula (A) were synthesized and screened for antimicrobial activity. (formula: see text) where: X = H (I, III, V, VII, IX, XI, XIII, XV), CH3 (II, IV, VI, VIII, X, XII, XIV, XVI); Y = H (I, II), 3-F (III, IV), 2-Cl (V, VI), 3-Cl (VII, VIII), 4-Cl (IX, X), 2-Br (XI, XII), 3-Br (XIII, XIV), 4-Br (XV, XVI). The synthetic approach involves the preparation of variously substituted Schiff-bases of indol-2,3-dione, which then are subjected to cyclocondensation with alpha-mercaptoalkanoic acids, to give spirothiazolidinones of type (A). The prepared compounds were screened against S. aureus, B. cereus, M. paratuberculosis, E. coli, S. typhi, Pr. mirabilis, Ps. aeruginosa, C. albicans, S. cerevisiae, A. niger by a disk-diffusion assay (Kirby-Bauer modified. The results of the antimicrobial screening showed that the prepared compounds exhibited varying degrees of activity against Gram-positive, Gram-negative bacteria, and fungi. 3-Fluoro-derivative (III) showed inhibitory activity especially toward S. aureus and C. albicans. Chloroderivatives (VII) and (VIII) showed broad-spectrum "in vitro" antimicrobial activity, and were especially inhibitory toward S. aureus, E. coli, and S. Typhi. Fluoro-derivative (IV) and bromo-derivatives (XIII) and (XIV) possessed marked antimicrobial activity against M. paratuberculosis.     

Antimicrobial activity of Securidaca longipedunculata

The folk herbal uses of Securidaca longipedunculata in the treatment of diarrhea, boils, gonorrhea, and cough prompted phytochemical analyses and antimicrobial activity screening of extracts of the root. Some flavonoids isolated showed activity against many micro-organisms. These flavonoids were isolated using chromatographic methods.     

A new structural alternative in benzo[b]furans for antimicrobial activity

Two series of 2-substituted and three new diacetyl benzofurans were synthesized through palladium-catalyzed reactions and their in vitro antimicrobial spectra were assessed. The compounds demonstrated mild to significant growth inhibition against antibiotic-susceptible standard and clinically isolated strains of Gram-positive and Gram-negative bacteria as well as human fungal pathogens. Ampicillin and kanamycin were used as references for antibacterial screening; nystatin and amphotericin B were used for antifungal screening. Varying substitution at the benzofuran moiety and subsequent antimicrobial screening identified the C-3-acetyl functionality as a new structural alternative for optimal antimicrobial property in the benzofuran class of compounds.     

A novel defensin‐like peptide from salivary glands of the hard tick,Haemaphysalis longicornis

A novel defensin‐like antimicrobial peptide named longicornsin was isolated from the salivary glands of the hard tick, Haemaphysalis longicornis, using a 10‐kDa cut‐off Centriprep filter and reversed‐phase high‐performance liquid chromatography (RP‐HPLC). Its amino acid sequence was determined as DFGCGQGMIFMCQRRCMRLYPGSTGFCRGFRCMCDTHIPLRPPFMVG by Edman degradation. The cDNA encoding longicornsin was cloned by cDNA library screening. The predicted protein from the cDNA sequence was composed of 78 amino acids including a mature longicornsin. It showed similarity with defensin‐like peptides from other ticks by BLAST search. Different from most other tick defensin‐like peptides, longicornsin had a C‐terminal extension. Purified longicornsin exerted potent antimicrobial activities against bacteria and fungi. Interestingly, it even showed strong antimicrobial ability against drug‐resistant microorganisms and Helicobacter pylori. The results of this study indicated that longicornsin is a potential candidate for novel antimicrobial drug design.     

Modulation of anti-pathogenic activity in canine-derived Lactobacillus species by carbohydrate growth substrate

AIMS: To investigate the effect of various carbon sources on the production of extracellular antagonistic compounds against two Escherichia coli strains and Salmonella enterica serotype Typhimurium by three canine-derived lactobacilli strains. METHODS AND MATERIALS: Cell-free preparations, pH neutralized, were used in antibiotic disc experiments as an initial screening. The bacteria/carbohydrate combinations that showed inhibition of the growth of those pathogens, were further investigated in batch co-culture experiments. The cell-free supernatants of the cultures, that decreased the population number of the pathogens in the co-culture experiments to log CFU ml-1 相似文献   

Improved antimicrobial activity of h‐lysozyme (107–115) by rational Ala substitution

The most challenging target in the design of new antimicrobial agents is the development of antibiotic resistance. Antimicrobial peptides are good candidates as lead compounds for the development of novel anti‐infective drugs. Here we propose the sequential substitution of each Ala residue present in a lead peptide with known antimicrobial activity by specific amino acids, rationally chosen, that could enhance the activity of the resultant peptide. Taking the fragment 107–115 of the human lysozyme as lead, two‐round screening by sequentially replacing both Ala residues (108 and 111) by distinct amino acids resulted in a novel peptide with 4‐ and 20‐fold increased antimicrobial activity against Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 29213, respectively. These results reinforce the strategy proposed, which, in combination with simple and easy screening tools, will contribute to the rapid development of new therapeutic peptides required by the market. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.     

An Escherichia coli cell membrane chromatography-offline LC-TOF-MS method for screening and identifying antimicrobial peptides from Jatropha curcas meal protein isolate hydrolysates

A novel, simple, and rapid method, named cell membrane affinity extraction (CMAE)-offline liquid chromatography time-of-flight mass spectrometry (LC-TOF-MS) was developed for screening and identifying antimicrobial peptides from Jatropha curcas meal protein isolate hydrolysates (JCMPIH) obtained by proteolytic enzyme (pepsin, trypsin, protamex, neutrase, flavourzyme, papain, alcalase, and acid protease) hydrolysis. A cationic antimicrobial peptide (CAILTHKR, JCpep8) was successfully isolated and identified by this method. Antimicrobial assay indicated that JCpep8 was active against the tested microorganisms (Escherichia coli ATCC 25922, Shigella dysenteriae ATCC 51302, Pseudomonas aeruginosa ATCC 27553, Staphylococcus aureus ATCC 25923, Bacillus subtilis ATCC 23631, Streptococcus pneumoniae ATCC 49619) with minimal inhibitory concentration values ranging from 29 to 68 μg/mL. JCpep8 induced significant morphological alterations of the tested microbe surfaces, as shown by transmission electron microscopy, indicating strong membrane disruption. The results showed that CMAE-offline LC-TOF-MS could be a promising method for discovering high-throughput screening antimicrobial peptides from JCMPIH.     

A novel antimicrobial peptide from skin secretions of the earthworm, Pheretima guillelmi (Michaelsen)

A novel lumbricin-like antimicrobial peptide named lumbricin-PG was isolated from skin secretions of the earthworm, Pheretima guillelmi (Michaelsen), using a procedure of one step Sephadex G-50 gel filtration and one step C₈ reverse-phase high-performance liquid chromatography (RP-HPLC). Its amino acid sequence was determined as FSRYARMRDSRPWSDRKNNYSGPQFTYPPEKAPPEKLIKWNN EGSPIFEMPAEGGHIEP by Edman degradation combined with cDNA cloning and mass spectrometry analysis. The cDNA encoding lumbricin-PG was cloned by cDNA library screening. The predicted protein from the cDNA sequence was composed of 73 amino acid residues including a mature lumbricin-PG and predicted signal peptide. It showed similarity with lumbricin antimicrobial peptide from the earthworm, Lumbricus rubellus by BLAST search. Purified lumbricin-PG exerted potential antimicrobial activities against bacteria and fungi; it showed weak hemolysis activity against human and rabbit red cells.     

Antimicrobial activity of lactic acid bacteria isolated from sour doughs: purification and characterization of bavaricin A, a bacteriocin produced by Lactobacillus bavaricus MI401

Three hundred and thirty-five lactic acid bacteria were isolated from sour doughs and screened for antagonistic activity. Of these 145 showed activity against one or several of the indicator strains used in the screening. The antimicrobial activity of 18 isolates were due to a proteinaceous compound. These 18 isolates belonged to three different Lactobacillus species: Lactobacillus bavaricus, Lactobacillus curvatus and Lactobacillus plantarum. The spectrum of antimicrobial activity for the three species suggested that the inhibitory components were different. The inhibitory compound from Lact. bavaricus MI401 was chosen for further study. The proteinaceous nature, antimicrobial activity against closely-related species, heat resistance and sensitivity to alkaline treatment strongly indicated that this substance was a bacteriocin, which we designated bavaricin A. The bacteriocin was purified to homogeneity by ammonium sulphate precipitation, ion exchange, hydrophobic interaction and reverse-phase chromatography. The purification resulted in 193000-fold increase in specific activity. SDS-PAGE of bavaricin A showed a molecular weight of 3500—4000 Da. By amino acid sequencing 41 amino acids were determined. Bavaricin A had a bactericidal mode of action and inhibited nine out of 10 Listeria monocytogenes. Lactobacillus bavaricus MI401 produced bavaricin A at temperatures from 4°C to 30°C. The production of active bavaracin A was inhibited at increasing sodium chloride concentration. In the presence of 3% sodium chloride at 4°C no active bavaricin A could be detected. Nitrite (100 ppm) did not affect the production of active bavaricin A.