Synthesis of new 1-alkyl-, 1-benzyl-, and 1-aryloxyethyl-substituted 4,5-dichloroimidazoles and their antimicrobial,protistocidal, and fungistatic properties

Previously unknown 1-alkyl-, 1-benzyl-, and 1-aryloxyethylderivatives of dichloroimidazoles and products of their structural transformation were synthesized from 4,5-dichloroimidazole or 2-methyl-4,5- dichloroimidazole using alkyl, benzyl or aryloxyethyl halides. These N-substituted compounds were shown to have a weak antibacterial activity against some pathogenic gram-positive and gram-negative bacteria (Staphylococcus aureus and Escherichia coli). At the same time, some of the obtained compounds demonstrated a significant protistocidal activity against Colpoda steinii, which can exceed in strength the activity of clinically used veterinary drug Baycox. Moreover, these compounds showed a pronounced fungistatic effect.     

Recyclization of 9-bromocotarnine under the action of haloacylhetarenes. Synthesis and biological activity of the 4-heteroaroyl-9-bromo-1,2-dihydro-6-methoxy-7,8-methylenedioxy-3-benzazepines

Reaction of 9-bromocotarnine with heterocyclic α-halo ketones is accompanied by the expansion of the six-membered dihydropyridine ring to seven-membered dihydroazepine one and leads to previously unknown 4-heteroaroyl-9-bromo-3-methyl-1,2-dihydro-6-methoxy-7,8-methylenedioxy-3-benzazepines. It has been shown that some of the resulting compounds exhibit a significant antibacterial activity against Staphylococcus aureus and Escherichia coli. At the same time, the synthesized benzazepines have shown no significant protistocidal activity against Colpoda steinii and fungistatic activity against Penicillium italicum.     

Synthesis of 9-bromocotarnine and its recyclization into 4-acyl-9-bromo-7,8-methylenedioxy-1,2-dihydro-3-benzazepines with anti-infective activity

9-Bromocotarnine in the stable perchlorate form has been obtained by the interaction of cotarnine with bromine. The reaction of 9-bromocotarnine with α-haloketones is accompanied by the extension of the six-membered hetero-ring to seven-membered ring and led to previously unknown 4-acyl-9-bromo-3-methyl-6-methoxy-7,8-methylendioxy-1,2-dihydro-3-benzazepines. Some of these compounds have been shown to have only moderate antibacterial (against Staphylococcus aureus, Escherichia coli) and fungistatic (Penicillium italicum) activities, but none of them has been shown to have a pronounced protistocidal activity against Colpoda steinii.     

Synthesis and antimicrobial activity of novel 1,4,5-triphenyl-1<Emphasis Type="Italic">H</Emphasis>-imidazol-[1,2,3]-triazole derivatives

Novel 1-phenyl-4-((4-(1,4,5-triphenyl-1H-imidazol-2-yl)phenoxy)methyl)-1H-1,2,3-triazole derivatives were synthesized by click chemistry reaction and screened for antimicrobial activity against grampositive and gram-negative bacterial and fungal species. All the compounds were characterized by ¹H and ¹³C NMR, IR, and mass spectral data. The results of antibacterial study indicated that 1-(4-nitrophenyl)-4-((4-(1,4,5-triphenyl-1H-imidazol-2-yl)phenoxy)methyl)-1H-1,2,3-triazole, 1-(4-(4-((4-(1,4,5-triphenyl-1H-imidazol-2-yl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)phenyl)ethanone, 1-(2,6-dichloro-4-nitrophenyl)-4-((4-(1,4,5-triphenyl-1H-imidazol-2-yl)phenoxy)methyl)-1H-1,2,3-triazole, and 1-(2-methoxy-4-nitrophenyl)-4-((4-(1,4,5-triphenyl-1H-imidazol-2-yl)phenoxy)methyl)-1H-1,2,3-triazole showed appreciable antibacterial activity while 1-(4-fluorophenyl)-4-((4-(1,4,5-triphenyl-1H-imidazol-2-yl)phenoxy) methyl)-1H-1,2,3-triazole, 1-(2,6-dichloro-4-nitrophenyl)-4-((4-(1,4,5-triphenyl-1H-imidazol-2-yl)phenoxy)methyl)-1H-1,2,3-triazole, and 1-(4-methoxyphenyl)-4-((4-(1,4,5-triphenyl-1H-imidazol-2-yl)phenoxy)methyl)-1H-1,2,3-triazole emerged as the most potential antifungal agents.     

A new 2-(4<Emphasis Type="Italic">H</Emphasis>-1,3-benzoxazin-4-on-2-yl)-1,3-tropolone: Synthesis,structure, and antibacterial properties

2-(4H-1,3-Benzoxazin-4-on-2-yl)-4,5,6-trichloro-1,3-tropolone, structural properties of which were studied using ¹H NMR, IR-spectroscopy, mass spectrometry, and quantum chemistry has been obtained for the first time using an acid-catalyzed condensation reaction of 3,4,5,6-tetrachloro-1,2-benzoquinone with 2-methyl-4H-3,1-benzoxazin-4-one. It has been shown that the new tropolone possesses antibacterial activity against hospital-acquired strains of gram-negative (Escherichia coli, Salmonella enterica sv. Enteritidis, Acinetobacter baumannii, and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) bacteria. The obtained substance is suggested for development of a new antibacterial drug.     

Synthesis of functionalized benzo[<Emphasis Type="Italic">f</Emphasis>]2<Emphasis Type="Italic">H</Emphasis>-chromenes and evaluation of their antimicrobial activities

Knoevenagel cyclocondensations of α-hydroxy naphthaldehyde with β-oxodithioesters and ketene dithioacetals yielded 2H-benzo[f]chromene-2-thiones and 2H-benzo[f]chromen-2-ones, respectively, in high yields. The newly synthesized compounds were evaluated for antifungal and antibacterial activities. Among them, compounds (2-furyl)(3-thioxo-3H-benzo[f]chromen-2-yl)methanone and phenyl(3-oxo-3H-benzo[f]chromen-2-yl)methanone exhibited excellent antifungal activity against tested fungi Curvularia lunata and Fusarium moniliforme. The highest antibacterial activity against the tested bacteria Escherichia coli and Staphylococcus aureus was observed for (4-chlorophenyl)(3-oxo-3H-benzo[f]chromen-2-yl)methanone. The results of antimicrobial screening demonstrate that (2-furyl)(3-thioxo-3H-benzo[f]chromen-2-yl)methanone, phenyl(3-oxo-3H-benzo[f]chromen-2-yl)methanone, and (4-chlorophenyl)(3-oxo-3H-benzo[f]chromen-2-yl)methanone are promising as antimicrobial drugs.     

Screening of lactic acid bacteria with cholesterol-lowering and triglyceride-lowering activity in vitro and evaluation of probiotic function

To screen the lactic acid bacteria with cholesterol-lowering and triglyceride-lowering activity in vitro and evaluate their probiotic function. By plate separating, cholesterol-lowering and triglyceride-lowering activity in vitro were determined; and by evaluating the probiotic functions, including tolerances to simulated gastric and intestinal juice, the antibacterial spectrum, and the adhesion ability to Caco-2 cells, the probiotic strains with cholesterol-lowering and triglyceride-lowering activity in vitro were screened, and then were identified by phenotypical and physiological tests and 16Sr DNA. Finally, the cholesterol-lowering and triglyceride-lowering activity in vivo of the strains were evaluated using male Sprague-Dawley rats. Two strains L2-16 and L2-73 with stronger cholesterol-lowering and triglyceride-lowering activity in vitro, stronger tolerance to simulated gastric and intestinal juice and adhesion ability to Caco-2 cells, and wider antibacterial spectrum were screened from traditional Chinese fermented cucumber and were identified as Lactobacillus acidophilus and Enterococcus faecalis, respectively. Compared with a hyperlipidemia diet without lactic acid bacteria, the diet supplemented with Lactobacillus acidophilus L2-16 and Enterococcus faecalis L2-73 significantly reduced serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol levels, and liver total cholesterol and triglyceride levels in rats (P?<?0.05). Moreover, the diet supplemented with Lactobacillus acidophilus L2-16 and Enterococcus faecalis L2-73 significantly increased the fecal elimination of bile acids (P?<?0.05). Lactobacillus acidophilus L2-16 and Enterococcus faecalis L2-73 may have application prospect in the production of some fermented foods such as fermented vegetables, milk, or meat, and probiotic preparations with the function to lower the serum lipid and liver lipid levels.     

Effect of selenium-containing biocomposites based on <Emphasis Type="Italic">Ganoderma</Emphasis> mushroom isolates grown in the presence of oxopropyl-4-hydroxycoumarins,on bacterial phytopathogens

Effect of selenium-containing biocomposites obtained from submerged cultures of macrobasidiomycetes Ganoderma applantum, G. cattienensis, G. colossus G. lucidum, G. neojaponicum, and G. valesiacum, on plant pathogenic bacteria Clavibacter michiganensis ssp. sepedonicus (Cms), Micrococcus luteus, Pectobacterium atrosepticum, Pectobacterium carotovorum subsp. carotovorum, Pseudomonas fluorescens, Pseudomonas viridiflava, and Xanthomonas campestris was studied. Oxopropyl-4-hydroxychromenones were used as components of the fungal nutrient media. The bacteriostatic and bactericidal activity of the Se-containing and Se-free substances of fungal origin against plant pathogenic bacteria was determined using colony-forming units count, the agar well diffusion method, and by turbidity measurements of bacterial suspensions. The composites produced from the extracellular metabolites of G. cattienensis SIE1302 with 4-hydroxy-3-(3-oxo-1,3-diphenyl propyl)-chromen-2-one (S(45)), and of G. lucidum SIE1303 with 4-hydroxy-3-(3-oxo-1-(3-nitrophenyl)-3-phenylpropyl)-chromen-2-one (S(NO₂)) possessed the most pronounced antibacterial action against Cms. The composites produced from the isolates of G. valesiacum 120702 with S(NO₂) showed the maximal antibacterial activity against Xanthomonas campestris B-610. High antimicrobial effect of G. lucidum 1315 with S(NO₂) against Xanthomonas campestris B-610 and of G. colossus SIE1301 against Pseudomonas fluorescens EL-2.1 was revealed. The pioneering information on the biological activity of coumarin series compounds in their application for producing the substances of fungal origin was obtained.     

Synthesis and antibacterial activity of some new benzo[5,6]chromeno[2,3-<Emphasis Type="Italic">d</Emphasis>]pyrimidines

The synthesis and antibacterial activity of some new benzo[5,6]chromeno[2,3-d]pyrimidine derivatives are described. The title compounds were obtained by the reaction of 1H-benzo[f]chromenes with aliphatic and aromatic amines. The structures of all newly synthesized compounds were confirmed by IR, ¹HNMR, ¹³C NMR, and NOESY experiments. The compounds exhibited potent antibacterial activity against gram-positive and gram-negative bacterial species. 10-Methyl-12-(4-hydroxyphenyl)-10,12-dihydro-11H-benzo[5,6]chromeno[2,3-d] pyrimidin-11-imine displayed greater antibacterial activity against gramnegative bacterial species than did ciprofloxacinandamoxicillin.     

Antimicrobial activities of some synthesized 1-(3-(2-methylphenyl)-4-Oxo-3<Emphasis Type="Italic">H</Emphasis>-quinazolin-2-yl-4-(substituted)thiosemicarbazide derivatives

The substituted thiosemicarbazide moiety was placed at the C-2 position and 2-methylphenyl group at N-3 position of quinazoline ring and obtained compounds were tested for their antitubercular activities and antibacterial activities against selected gram-positive and gram-negative bacteria. The target compounds 1-(3-(2-methylphenyl)-4-oxo-3H-quinazolin-2-yl)-4-(substituted) thiosemicarbazides were obtained by the reaction of 2-hydrazino-3-(2-methylphenyl) quinazolin-4(3H)-one with different dithiocarbamic acid methyl ester derivatives. All synthesized compounds were also screened for their antimicrobial activity against selective gram-positive and gram-negative bacteria by agar dilution method. Among the series, 1-[3-(2-methylphenyl)-4-oxo-3H-quinazolin-2-yl]-4-[4-chlorophenyl]-thiosemicarbazide exhibited the most potent activity against S. typhi, E. coli, and B. subtilis, while 1-[3-(2-methylphenyl)-4-oxo-3H-quinazolin-2-yl]-4-[4-nitrophenyl]-thiosemicarbazide was the most potent against E. coli, B. subtilis, P. aeruginosa, S. typhi, and S. flexneri. These two compounds exhibited the antitubercular activity at the minimum concentration (3 μg/mL) that offered potential for further optimization and development of new antitubercular agents. The obtained results demonstrated promising antimicrobial and antitubercular activities of the synthesized quinazoline compounds which could be used as new scaffolds for improving their antimicrobial activity.     

Effect of salt stress on the antimicrobial activity of <Emphasis Type="Italic">Ruta chalepensis</Emphasis> essential oils

In the current investigation, the biological activities of essential oils obtained from organs of Ruta chalepensis plants grown under salt stress (0, 50 and 100 mM NaCl) were analyzed. Their chemical composition was often investigated by GC/FID and GC–MS and the antimicrobial activities towards eight bacteria (Salmonella All, Salmonella K, Escherichia coli 45AG, Escherichia coli 45AI, Staphylococcus aureus 9402, Staphylococcus aureus 02B145, Listeria 477 and Pseudomonas aeruginosa ATCC 10145) and five fungi strains (Aspergillus, Saccharomycee crvisiale, Streptomyces griseus, Fusarium solani and Penicillium thomii) were studied. Results revealed that salt increased essential oil production in leaves at 50 and 100 mM NaCl. A total of 20 compounds were identified in leaves, undecan-2-one, nonan-2-one and geijerene being the dominant ones. In stems, 21 compounds were found; they were dominated by decan-2-one, geijerene, nonan-2-one and undecan-2-one. In contrast, roots exhibited a large variation with 25 volatile compounds and octyl acetate, methyl decanoate, phytyl acetate were the major ones. Salt stress induced significant antibacterial activity changes, mainly in leaves and stems. In leaves, the minimum inhibitory and bactericidal concentration decreased at 100 mM NaCl against Listeria 477, the two strains of E. coli (45AG and 45AI) and P. aeruginosa but it increased versus other bacteria. In stems, salt increased oil antibacterial activity against all strains except P. aeruginosa ATCC 10145. Root oil showed the least antibacterial activity under saline conditions versus Listeria 477 and P. aeruginosa ATCC 10145. As regards antifungal activity, NaCl reduced the antifungal activity of essential oils against the majority of fungi strains.     

Calcium-dependent antibacterial activity of donkey’s milk against <Emphasis Type="Italic">Salmonella</Emphasis>

The aim of this study was to examine the antibacterial activity of raw donkey’s milk (DM) against Salmonella Enteritidis and Salmonella Typhimurium as well as to determine the dependence of this antibacterial activity on calcium, lysozyme and lactoferrin content. Antibacterial assays were conducted in DM artificially contaminated with these Salmonella serotypes and then incubated at 38 °C for 8 hours. Calcium concentration was found to have a strong influence on the antibacterial activity of the contaminated DM samples supplemented with CaCl₂ and EDTA. The antibacterial activity of DM against the tested Salmonella strains was observed to be strongly calcium dependent, with the addition of CaCl₂ to DM samples improving its antibacterial potential against both pathogens. Salmonella Enteritidis appeared to be less sensitive to the antimicrobial agents in DM than S. Typhimurium. One explanation is the calcium-dependant antibacterial activity of DM is attributable to the calcium-binding ability of its lysozyme. Lysozyme may be the main antibacterial agent, most probably via a nonenzymatic mode of action against tested Salmonella strains.     

Synthesis and Protective Activity of β-Glycosides of <Emphasis Type="Italic">N</Emphasis>-Acetylmuramyl-<Emphasis Type="Italic">L</Emphasis>-Alanyl-<Emphasis Type="Italic">D</Emphasis>-Isoglutamine with Alkylalicyclic and Arylaliphatic Aglycons

The following glycosides of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) were synthesized: β-4-tert-butylcyclohexyl MDP, β-2-(adamant-1-yl)ethyl MDP, β-2,2-diphenylethyl MDP, and β-2-(p-biphenyl) ethyl MDP. The starting peracetylated β-N-acetylglucosaminides were prepared by the oxazoline method. They were converted into 4,6-O-isopropylidene-N-acetyl-D-muramic acids, which were coupled with L-Ala-D-Glu(NH₂)OBn. The target glycopeptides were obtained after their deprotection. The stimulation of the anti-infection resistance of mice against Staphylococcus aureus by the MDP glycosides was studied.     

The Phenolic Contents and Antimicrobial Activities of Some Marine Algae from the Mediterranean Sea (Algeria)

In this study, three marine algae collected from western coast of algerian mediteranean sea (Ulva lactuca, Dictyota dichotoma, and Corallina elongata) were tested using the agar-well diffusion method for their production of antibacterial and antifungal agents on various organisms that cause diseases of humans and plants (Eschirichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, Salmonella sp, Candida albicans, and Penicillium sp.). The total phenol content and antimicrobial activity were determined using different crude seaweeds extracts (methanol, diethylether, and chloroform). The results show that the chloroform extracts of (Ulva lactuca and Corallina elongata) had the highest activity against E. coli and Salmonella sp. The methanol extract obtained from (Ulva lactuca, Dictyota dichotoma, and Corallina elongata) showed antifungal activity for Candida albicans. The results of the study revealed that the seaweeds from Algeria appear to have immense potential as a source of antibacterial and antifungal compounds; they can be used in treating diseases caused by these organisms.     

Synthesis and Anti-Infective Activity of 2-Heteroaryl(Acyl)-9,10,12,13-Tetramethoxy-3-Methyl-4,5-Dihydro-3<Emphasis Type="Italic">H</Emphasis>-Phenanthro[1,2-<Emphasis Type="Italic">d</Emphasis>]Azepines

2-Hetaryl- and 2-acyl-9,10,12,13-tetramethoxy-3-methyl-4,5-dihydro-3H-phenanthro[1,2-d]-azepines have been synthesized from 8,9,11,12-tetramethoxy-2-methyl-3,4-dihydronaphtho[2,1-f]isoquinolinium perchlorate by pyridine-azepine recyclization. The resulting compounds have revealed a pronounced antibacterial activity against Staphylococcus aureus (strain P-209) and Escherichia coli (field strain 078). Some of these compounds have a moderate fungistatic activity against Peniciliium italicum fungi. Two compounds have shown a certain activity in relation to the Colpoda steinii protozoa.     

Pancreatic lipase inhibitory activity of monogalactosyldiacylglycerols isolated from the freshwater microalga <Emphasis Type="Italic">Chlorella sorokiniana</Emphasis>

Chemical investigation of the freshwater microalga Chlorella sorokiniana led to the isolation of a monogalactosyldiacylglycerol (MGDG)-rich fraction possessing dose-dependent inhibitory activity against pancreatic lipase activity. The MGDG-rich fraction contains 12 MGDGs identified by LC/HRMS analysis. Among them, three MGDGs were new compounds, namely, (2S)-1-O-(7Z,10Z-hexadecadienoyl)-2-O-(7Z,10Z,13Z-hexadecatrienoyl)-3-O-β-D-galactopyranosylglycerol (1), (2S)-1-O-linoleoyl-2-O-(7Z,10Z-hexadecadienoyl)-3-O-β-D-galactopyranosylglycerol (6), and (2S)-1-O-oleoyl-2-O-(7Z,10Z-hexadecadienoyl)-3-O-β-D-galactopyranosylglycerol (8). The major galactolipids were isolated by semipreparative HPLC and tested for their effect toward pancreatic lipase inhibitory activity. All the tested MGDGs showed significant reduction of pancreatic lipase activity indicating possible beneficial use for management of lipase-related disorders such as obesity.     

Fusion expression of the PGLa-AM1 with native structure and evaluation of its anti-<Emphasis Type="Italic">Helicobacter pylori</Emphasis> activity

Helicobacter pylori (H. pylori) shows increasingly enhanced resistance to various antibiotics, and its eradication has become a major problem in medicine. The antimicrobial peptide PGLa-AM1 is a short peptide with 22 amino acids and exhibits strong antibacterial activity. In this study, we investigated whether it has anti-H. pylori activity for the further development of anti-H. pylori drugs to replace existing antibiotics. However, the natural antimicrobial peptide PGLa-AM1 shows a low yield and is difficult to separate, limiting its application. A good strategy to solve this problem is to express the antimicrobial peptide PGLa-AM1 using gene engineering at a high level and low cost. For getting PGLa-AM1 with native structure, in this study, a specific protease cleavage site of tobacco etch virus (TEV) was designed before the PGLa-AM1 peptide. For convenience to purify and identify high-efficiency expression PGLa-AM1, the PGLa-AM1 gene was fused with the polyhedrin gene of Bombyx mori (B. mori), and a 6 × His tag was designed to insert before the amino terminus of the fusion protein. The fusion antibacterial peptide PGLa-AM1 (FAMP) gene codon was optimized, and the gene was synthesized and cloned into the Escherichia coli (E. coli) pET-30a (+) expression vector. The results showed that the FAMP was successfully expressed in E. coli. Its molecular weight was approximately 34 kDa, and its expression level was approximately 30 mg/L. After the FAMP was purified, it was further digested with TEV protease. The acquired recombinant antimicrobial peptide PGLa-AM1 exerted strong anti-H. pylori activity and therapeutic effect in vitro and in vivo.     

Synthesis of some new <Emphasis Type="Italic">N</Emphasis>-substituted-<Emphasis Type="Italic">N</Emphasis>-(2,3-Dihydro-[1,4]benzodioxin-6-yl)-4-acetamidobenzenesulfonamides as valuable antibacterial agents

The aim of the research was to investigate the anti-bacterial potential of some N-substituted sulfonamides bearing benzodioxane moiety. The synthesis was started by reaction of N-2,3-dihydrobenzo[1,4]dioxin-6-amine with 4-acetamidobenzene-1-sulfonyl chloride in the presence of 10% aqueous Na₂CO₃ solution to yield N-(2,3-dihydrobenzo[1,4]-dioxin-6-yl)-4-acetamidobenzenesulfonamide, which was further reacted with alkyl/aralkyl halides in DMF and lithium hydride as a base to afford N-substituted-N-(2,3dihydro-[1,4]-benzodioxin-6-yl)-4-acetamidobenzenesulfonamides. All the synthesized compounds were characterized by spectral data (IR, ¹H NMR, EI-MS, and HR-MS). The compounds were tested for antibacterial activity and most of them exhibited potent therapeutic potential against various Gram-negative and Gram-positive strains.     

Antarctic red macroalgae: a source of polyunsaturated fatty acids

The n-3 and n-6 series of polyunsaturated fatty acids (PUFAs) are important for numerous metabolic functions that reduce the risk of inflammation, cancer, and heart diseases. These fatty acids (FAs) have been detected in high concentrations in some species of algae. The amount of the n-3 and n-6 PUFAs is closely associated with abiotic factors, such as solar radiation intensity, salinity, and temperature variation. However, abiotic influence on PUFA levels, along with the physiological function of these molecules in algae, remains inconclusive. In the present study, the quantities of the n-3 and n-6 in Antarctic red algae species Iridaea cordata, Palmaria decipiens, Plocamium cartilagineum, and Pyropia endiviifolia were determined. The lipids were extracted from the macroalgae according to the method followed by Bligh and Dyer (1959) and converted to methyl esters for further analysis using gas chromatography. The main n-6 PUFA identified and quantified in this study of Antarctic red algae were linoleic acid (18:2n-6), dihomo-γ-linolenic acid (20:3n-6), and arachidonic acid (20:4n-6). The eicosapentaenoic acid was detected at high concentrations in all species, with approximately 62.8% of total FA in P. endiviifolia, 75.4% in P. decipiens, 50.4% in I. cordata, and 20.1% in P. cartilagineum. The results corroborate those of the literature and show that PUFAs increased in red algae environments, with increased production of n-3 and n-6 PUFAs.