Synthesis and antimicrobial evaluation of some fused heterocyclic [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives

A series of fused 1,2,4-triazoles with diphenylsulfone moiety are prepared utilizing 4-amino-5-[4-(4-X-phenylsulfonyl)phenyl]-4H-1,2,4-triazole-3-thiol 1 (X=H, Br). The latter on reaction with aromatic isothiocyanate in DMF, aromatic acid in POCl3 and CDI in dioxane gives five membered fused triazole derivatives 2a-c, 3a-c, 4a-g, 5a-g and 6a,b. The structures of newly synthesized compounds were confirmed on the basis of their elemental analysis and spectral data results (IR, 1H-and 13C NMR). New synthesized compounds were screened for their antimicrobial activities. The preliminary results revealed that some of the compounds exhibited promising antimicrobial activities.     

Biological properties of arginine-based gemini cationic surfactants

Biological properties of novel gemini (double-chain/double-head) cationic surfactants, Nalpha,Nomega-bis(Nalpha-acylarginine)alpha,omega-alkylendiamides, so-called bis(Args), are reported. The effect of both the alkyl (10 and 12 carbon atoms) and the spacer chain (from 2-10 methylene groups) of bis(Args) on their antimicrobial activity, acute toxicity on Daphnia magna and Photobacterium phosphoreum, and aerobic biodegradability is studied. These surfactants constitute a novel class of chemicals of low toxicity with excellent surface properties and considerable antimicrobial activity. The aquatic toxicity of these compounds is lower than that of the conventional Monoquats. As regards the biodegradation test, the molecules with a spacer chain < or =6 methylene groups can be considered as ready biodegradable. The increase of hydrophobicity in the bis(Args) is a negative structural parameter for their environmental behavior.     

Antimicrobial activity of commercial citrus-based natural extracts against Escherichia coli O157:H7 isolates and mutant strains

Due to increasing concerns about the development of antimicrobial resistance amongst pathogenic bacteria, alternative strategies have been sought that do not use antibiotics to reduce pathogenic bacteria from foods and patients. A natural compound that has potent antimicrobial properties is citrus peel, which contains a variety of essential oils that inhibit the growth of or kill pathogenic bacteria. In the present study, seven citrus-based natural antimicrobials were evaluated for their ability to inhibit the growth of the pathogen Escherichia coli O157:H7. Zones of inhibition of E. coli O157:H7 by the citrus-derived fraction (10 microL/6 mm disk) were determined by a disk-diffusion assay on Sorbitol-MacConkey agar. Inhibition zones were observed after 48 h lawn growth of E. coli O157:H7 cells at 37 degrees C. Two citrus-based fractions, orange CP VAL terpeneless FAB 968611 and Limonene 1x Dist FAB 955430, inhibited E. coli O157:H7 with inhibition zones of approx. 11-24 mm dia. The remaining other five citrus-derived extracts (orange oil FL VAL 1121 ARR 974760, Orange 5x Conc VAL 4121 ARR 968374, orange terpenes ESS 1120 ARR 986259, orange terpenes CP 1100 ARR 986255, and orange terpenes OEO HP 1100 ARR 986257) were noninhibitory to E. coli O157:H7, yielding no clear inhibition zones. These studies show that citrus-derived natural compounds differ in their inhibitory activity against E. coli O157:H7 and some have potential applications as inhibitory agents against E. coli O157:H7 in various pathogen reduction strategies.     

Interaction of vitamin E and its model compounds with unsaturated fatty acids in homogeneous solution

Either alpha-tocopherol (vitamin E) or one of its model compounds having side chains of different length at the 2-position of alpha-tocopherol, forms complexes with an unsaturated fatty acid in methanol. For complex formation, the isoprenoid side chain and hydroxy group of alpha-tocopherol are unessential and, rather, the methyl groups attached to the aromatic ring of the chromanol moiety seems to be responsible. For better interaction, more than three methylene-interrupted Z double bonds of a fatty acid are necessary. These findings are incompatible with the hypothesis of Diplock and Lucy on the interaction of vitamin E with each polyunsaturated fatty acid.     

葡萄干提取物对两种耐药菌的ESBLs活性抑制作用评价

为寻找天然抗菌药物,在前一阶段试验结果的基础上,选用合适方法浸提葡萄干活性成分,针对耐药性强的革兰阳性金黄色葡萄球菌及革兰阴性铜绿假单胞菌的ESBLs抑制作用以及最低抑菌浓度(MIC)加以评价。实验结果显示,葡萄干提取物对金黄色葡萄球菌及铜绿假单胞菌的ESBLs活性均有明显抑制作用,从最低抑菌浓度反应出,葡萄干提取液对铜绿假单胞菌的抑杀能力强。说明葡萄干提取物中有可以抑杀病原菌的成分,也为从葡萄干中获得有效成分抑杀耐药菌开拓了思路。     

Novel cephalosporin derivatives possessing a substituted cinnamoyl moiety at the 7 beta-position. Synthesis, structural characterization and antibacterial activity of 3-acetoxymethyl cephalosporin derivatives

Twenty 3-acetoxymethyl cephalosporin derivatives, with various cinnamoyl (3-phenyl-2-propenoyl) substituted groups at the 7beta-position, were synthesized and evaluated for antibacterial activity in vitro. Some of these cephalosporin derivatives showed good selective activity against Gram-positive bacteria. Although substitution on the aromatic ring of cinnamoyl moiety generally reduced antimicrobial activity against Staphylococcus sp. and Enterococcus sp., a hydroxy group at the para position, and particularly ortho, para di-chloro substitution, improved the activity against methicillin resistant strains of Staphylococcus aureus (MRSA). Substitution on the double bond alpha position of the cinnamoyl moiety also affected the antimicrobial activity. A cyano group attached to this position increased activity against both negative coagulase Staphylococcus and Enterococcus sp. and extended the antibacterial spectrum towards Gram-negative bacteria.     

Synthesis, physicochemical properties and antimicrobial activity of some new benzimidazole derivatives

Some derivatives of benzimidazole were synthesized by nucleophilic substitution of 2-substituted-1H-benzimidazole. The resulting ethyl (2-substituted-1H-benzimidazol-1-yl) acetate on treatment with hydrazine hydrate yielded 2-(2-substituted-1H-benzimidazol-1-yl) acetohydrazide, which on further reaction with one equivalent of different aliphatic or aromatic carboxylic acids in the presence of phosphoryl chloride afforded the corresponding target compounds, 2-substituted-1-[{(5-substituted alkyl/aryl)-1,3,4-oxadiazol-2-yl} methyl]-1H-benzimidazole. The structures of the synthesized compounds were evaluated by spectral and elemental methods of analyses. All the synthesized compounds were screened for their antimicrobial activities. All of the derivatives showed good activity towards Gram-positive bacteria and negligible activity towards Gram-negative bacteria. Some of the synthesized compounds showed moderate activity against tested fungi.     

Antimicrobial peptides in mucosal secretions: the importance of local secretions in mitigating infection

The antimicrobial activity of the collective molecules comprising human milk reflects an evolutionarily successful paradigm for preventing and limiting microbial infection. Understanding the molecules that participate in this process and how they work can yield insight into potentially new antimicrobial therapies. Upon proteolytic processing, antimicrobial peptides can be derived from milk proteins, such as lactoferrin, casein, and lysozyme. Similarly, using the HIV-1 gp41 protein template, we have demonstrated that the 28-residue C-terminus, when produced as an independent peptide, exhibits selective toxicity for bacteria over eukaryotic cells. Upon optimizing this sequence for cationic charge and hydrophobic character presented as a alpha-helical structure, we show improved capability of the parent LLP1 sequence to selectively kill bacteria in the host environment and that this activity is increased by the inclusion of Trp residues on the hydrophobic face. We report that it is possible to (i) design de novo antimicrobial peptides that demonstrate optimal antimicrobial activity with minimal inflammatory activity and (ii) design antimicrobial peptides to function in a defined environment. In the end, we describe a de novo designed antimicrobial peptide, WLBU2, which is selectively toxic to microbial pathogens in complex environments and does not stimulate a significant immunomodulatory response. In spite of these properties, WLBU2 activity against Pseudomonas aeruginosa in human milk is inferior to the host peptide LL37 with regard to antimicrobial potency. These studies demonstrate that antimicrobial peptides can be engineered for greater potency in one medium but may not be optimal for working in a different medium such as human milk.     

Nutrition and health--toxic substances in food

With respect to food, the most important factors causing adverse health effects are: an unbalanced diet, resulting in obesity or vitamin deficiencies, overconsumption of alcohol or fat, the presence of microbial contamination and the presence of natural toxins. Two additional factors, the presence of environmental contaminants and products formed on heating food, may also be of importance. It is generally assumed that, when combined, food-related factors contribute to around 35% of overall cancer incidence. The most important groups of health-threatening compounds to be found in the food chain include natural toxins, such as those produced by plants (phytotoxins), fungi (mycotoxins), marine algae (phycotoxins) and by bacteria, and toxins present in animals for human consumption, especially fish. A second important group of toxic compounds in food consists of environmental contaminants, including heavy metals and persistent organic pollutants, such as dioxins and polychlorinated biphenyls, all of which may unintentionally end up in the food chain. A third group of toxins present in food are those substances produced when food is heated, and include polycyclic aromatic hydrocarbons, heterocyclic amines and acrylamide.     

Synthesis and antimicrobial activities of some new triazolothiadiazoles bearing 4-methylthiobenzyl moiety

A series of substituted triazolothiadiazoles have been synthesized by condensing 4-amino-3-[4-methylthiobenzyl]-4H-1,2,4-triazole-5-thiol (5) with substituted aryl furoic acids/aromatic acids in the presence of POCl3. The triazole (5) was obtained by the fusion of 4-methylthiophenyl acetic acid with thiocarbohydrazide. The structures of newly synthesized compounds are characterized by elemental analysis, IR, 1H NMR and mass spectroscopic studies and were screened for their antimicrobial activities. The preliminary results revealed that some of the compounds exhibited promising antimicrobial activities.     

Antileukotrienic phenethylamido derivatives of arylalkanoic acids in the treatment of ulcerative colitis

A series of arylalkanoic acid derivatives bearing methyl(phenethyl)amino groups were prepared and their inhibition of LTB(4) biosynthesis was evaluated. Regression analysis showed the slightly different parabolic dependences of this activity on lipophilicity of alpha-methyl and alpha-unsubstituted alkanoic acid derivatives. The relationship derived for alpha-unsubstituted alkanoic acids was extended by previously prepared group of similar derivatives of arylacetic acids without any change of regression coefficients and statistical criteria. It was concluded that the most active compounds belong to 2-arylpropanoic acid derivatives with lipophilicity close to logP(opt) (=6.97). But generally, the structural changes in the acidic part of compounds under study did not yield the substantial improvement of LTB(4) biosynthesis inhibition in comparison with the previously prepared series of derivatives IV. The anti-inflammatory effect of the compounds under study was evaluated in three animal models of inflammation and their possible utilization in the treatment of ulcerative colitis (UC) was followed. From 12 evaluated compounds, 4 compounds are more active in UC inhibition than the standard sulfasalazine but it can be stated that the change of connecting chain between aromatic ring and carboxyl did not bring about the important improvement of this activity in comparison with previous derivatives of arylacetic acids. Possible relation between LTB(4) biosynthesis inhibition and ulcerative colitis is seriously broken by the compound 8a with carbonyl as the additional functional group on the connecting chain between carboxyl and aromatic ring.     

Synthesis, spectroscopic and biological properties of bis(3-arylimidazolidinyl-1)methanes. A novel family of antimicrobial agents

Synthesis, spectroscopic and biological properties of new bis(3-arylimidazolidinyl-1)methanes are described. These compounds were synthesized by condensation reaction between N-arylethylenediamines and formaldehyde. Chemical structures were confirmed by means of their (1)H- and (13)C-NMR and mass spectroscopic data. Investigation of in vitro antimicrobial activity was performed using Gram-negative and Gram-positive bacteria as well as antifungal studies against Aspergillus niger and Candida albicans. Minimal inhibitory concentrations of active compounds were determined.     

Influence of weaning on fecal shedding of pathogenic bacteria in dairy calves

The objectives of the current research were to determine the effect of weaning on fecal shedding of Salmonella and Escherichia coli O157:H7 in dairy calves and to examine cultured isolates (to include Enterococcus) for antimicrobial susceptibility. This research was conducted on one large commercial dairy (>3000 head) in the southwestern United States. Two collections were made, during the winter (January 2009) and summer (July 2009) seasons. For the winter collection, two groups of calves were sampled (group 1: n?=?18 pens, 69 head, ～12 weeks of age; group 2: n?=?19 pens, 75 head, ～10 weeks of age). Fecal samples were collected from all calves via rectal palpation 2 days pre- and again 2 days postweaning. For the summer collection, one group of calves housed in 40 pens were utilized and 79 and 76 calves sampled 7 days pre- and 5 days postweaning, respectively. Fecal samples were collected into sterile palpation sleeves, placed on ice, and shipped to our laboratory for bacterial culture of E. coli O157:H7, Salmonella, and Enterococcus. Antimicrobial susceptibility was determined on select isolates. No differences (p?>?0.10) in prevalence of Salmonella or E. coli O157:H7 were observed due to weaning in the winter collection. In the summer collection, more (p?相似文献   

Effect of molecular structures on the solubility enhancement of hydrophobic organic compounds by environmental amphiphiles

Amphiphilic molecules, such as humic substances and surfactants, are known to increase the apparent aqueous solubility of hydrophobic organic compounds (HOCs) in the aqueous phase because of their molecular structures, which consist of hydrophilic and hydrophobic moieties. In this study, we examined the effect of the structures of humic acid and HOCs on the sorption of four polycyclic aromatic hydrocarbons (PAHs) and an organochlorine pesticide, p,p'-DDT, to humic acid. As the number of aromatic rings was increased, the extent of solubility enhancement of PAHs by humic acid was increased. Although p,p'-DDT was more hydrophobic than pyrene in this study, the extent of solubility enhancement of p,p'-DDT by humic acid was lower than that of pyrene because of the molecular structures of the solutes. Anionic surfactants with and without aromatic rings also were studied for comparison, and the dianionic surfactant with two benzene rings exhibited similar results with humic acid, unlike the surfactants without and with one benzene ring. The results from this study indicate that bulky molecules, such as p,p'-DDT sorbed with more difficulty to the aggregates of amphiphiles with larger molecules, such as humic substances and the dianionic surfactants.     

Degradation of btex compounds under iron-reducing conditions in contaminated aquifer microcosms

The potential for benzene, toluene, ethylbenzene, and xylenes (BTEX) degradation was investigated in microcosms inoculated with sediment and groundwater from a polluted iron-reducing aquifer. Benzene, toluene, and each of the three xylene isomers were degraded by the intrinsic microorganisms under iron-reducing conditions, but there was no removal of ethylbenzene. This work provides the first evidence for para-xylene degradation by dissimilatory iron-reducing bacteria. Microcosms adapted to benzene, toluene, or m-xylene were subsequently exposed to a different BTEX compound, which was degraded without lag phase, suggesting that the same group of bacteria could be involved in the removal of more than one BTEX compound. Furthermore, when microcosms were exposed to a mixture of BTEX, concurrent degradation of benzene and toluene, but not of meta-xylene and ethylbenzene, was observed. These results suggest that, under the influence of the plume of pollution, an iron-reducing microbial community able to degrade multiple aromatic compounds has developed.     

A facile, one-pot synthesis, characterization and antimicrobial activity of o-hydroxy anilide derivatives and 1-substituted-1,3-dicyclohexylurea analogs of long chain carboxylic acids

A series of novel o-hydroxy anilide derivatives and 1-substituted-1,3-dicyclohexylurea analogs of long chain carboxylic acids have been synthesized. The structures of the synthesized compounds were elucidated by IR, ¹H NMR, ¹³C NMR and mass spectral data. All the synthesized compounds were tested for their antimicrobial activity by disk diffusion assay with slight modifications 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 all the tested compounds showed moderate to good microbial inhibitions. Compounds 3e, 4e, 3f and 4f were found to be the most potent antimicrobial agents.     

Chemoenzymatic synthesis and antimicrobial activity evaluation of monogalactosyl diglycerides

Monogalactosyl diglycerides with medium to long fatty acid acyl chains, were prepared and examined for antimicrobial activity against Gram positive, Gram negative bacteria and fungi. The study of their in vitro antimicrobial activity confirms the significant activity of some monogalactosyl diacylglycerol analogues and establishes for the galactose series that the 1,2-disubstitution and the octanoyl chain are the proper structural features for the maximum activity.     

Antibacterial and antifungal activities of new pyrazolo[3,4-d]pyridazin derivatives

Several new pyrazolo[3,4-d]pyridazin derivatives were prepared by the reaction of two [corrected] 1H-pyrazole-3-carboxylic acids and various hydrazines. The compounds were tested for antimicrobial activities against Gram-negative, Gram-positive bacteria and fungi. The compounds named as 7e, f had the highest antimicrobial activities against Gram-negative, Gram-positive bacteria and fungi with minimum inhibitory concentrations in the range of 0.31 to<0.0024 mg ml(-1) .     

The prevalence of antimicrobial resistance in human faecal flora in South Africa.

Between January and March 1992, 361 faecal specimens were collected from the healthy black population in the Transvaal Province of South Africa. Each specimen was examined for the prevalence of antimicrobial resistance in commensal bacteria. Volunteers, from both rural and urban dwellings, were divided into four age groups. The overall carriage rate of resistance varied from 88.6% for ampicillin, 74.2% for trimethoprim, 52.6% for chloramphenicol, 10.2% for nalidixic acid to 7.5% for gentamicin. The carriage of resistance found to each individual antimicrobial agent was slightly higher in the rural population rather than the urban population but there was no correlation between the prevalence of antimicrobial resistance and the age group.     

Wirkmechanismen von Antibiotika und bakterielle Resistenz

Antibiotics are indispensable for the treatment of bacterial infections and to prevent or treat infections in invasive medical procedures. They arrest bacterial growth or kill them without harming their host. The cause for this high selectivity is that bacterial and mammalian cells differ substantially in their molecular structures. However, within the last 2–3 decades bacteria have developed strategies to defend antibiotics. Due to the unrestricted use of antibiotics multiresistant bacteria have been selected in medical facilities such as hospitals. For some of these multiresistant bacteria no treatment is available and patients must die. As the introduction of new antibiotics cannot cope with the speed of bacteria becoming resistant physicians must rigorously change their practical use of antibiotics. Only the restricted and professional use of antibiotics will preserve their beneficial effects. The aim of this article is to provide basic microbiological facts for readers who are not familiar with antimicrobials und bacterial resistance. After reading this article the reader should be able to understand the following articles of this specific issue: “Antibiotics and antibiotic resistance in urban waste water”. Mechanisms of action of the most important groups of antimicrobials as well as the development of bacterial resistance against certain antimicrobial agents are shown in exemplary fashion.