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161.
A. A. Romani M. C. Baroni S. Taddei F. Ghidini P. Sansoni S. Cavirani C. S. Cabassi 《Journal of peptide science》2013,19(9):554-565
Antimicrobial‐peptide‐based therapies could represent a reliable alternative to overcome antibiotic resistance, as they offer potential advantages such as rapid microbicidal activity and multiple activities against a broad spectrum of bacterial pathogens. Three synthetic antimicrobial peptides (AMPs), AMP72, AMP126, and also AMP2041, designed by using ad hoc screening software developed in house, were synthesized and tested against nine reference strains. The peptides showed a partial β‐sheet structure in 10‐mM phosphate buffer. Low cytolytic activity towards both human cell lines (epithelial, endothelial, and fibroblast) and sheep erythrocytes was observed for all peptides. The antimicrobial activity was dose dependent with a minimum bactericidal concentration (MBC) ranging from 0.17 to 10.12 μM (0.4–18.5 µg/ml) for Gram‐negative and 0.94 to 20.65 μM (1.72‐46.5 µg/ml) for Gram‐positive bacteria. Interestingly, in high‐salt environment, the antibacterial activity was generally maintained for Gram‐negative bacteria. All peptides achieved complete bacterial killing in 20 min or less against Gram‐negative bacteria. A linear time‐dependent membrane permeabilization was observed for the tested peptides at 12.5 µg/ml. In a medium containing Mg2+ and Ca2+, the peptide combination with EDTA restores the antimicrobial activity particularly for AMP2041. Moreover, in combination with anti‐infective agents (quinolones or aminoglycosides) known to bind divalent cation, AMP126 and AMP2041 showed additive activity in comparison with colistin. Our results suggest the following: (i) there is excellent activity against Gram‐negative bacteria, (ii) there is low cytolytic activity, (iii) the presence of a chelating agent restores the antimicrobial activity in a medium containing Mg2+ and Ca2+, and (iv) the MBC value of the combination AMPs–conventional antibiotics was lower than the MBC of single agents alone. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
162.
A mechanistic model is presented for determination of antimicrobial presence in the environment, using antimicrobial characteristics and Irish-specific usage data. The model simulates release of antimicrobials into the aquatic environment by integrating the effects of antimicrobial use, metabolism, degradation, and dilution. Predicted environmental concentrations (PECs) were ranked in relation to their potential to select for resistant bacteria, toxicity (chronic and acute), and hazard quotient (HQ). The simulated mean PECs of penicillins (PEN), β-lactams (BET), tetracyclines (TET), macrolides (MAC), quinolone/fluoroquinolones (Q/F), and sulphonamides/trimethoprim (S/T) were 1.05, 0.19, 0.06, 0.07, 0.02, and 0.08 mg/m3, respectively. All antimicrobials, excluding Q/F, showed a low HQ (<1) indicating low toxicity. Q/F had a HQ of 1.51 indicating moderate toxicity. All antimicrobial groups expressed varying resistance formation potential with Q/F having the highest. Q/F also exhibited the lowest degradation rate. A sensitivity analysis indicated a possible role for considering metabolism during regulation of new antimicrobials as this can significantly influence PEC values. The observed results suggest that current antimicrobial use can lead to levels in the environment that may increase resistance formation. The results and limitations presented here accentuate the need for further investigation into antimicrobials in the environment and contribution to resistant strains. 相似文献
163.
164.
Abstract We quantified the effects of anthropogenic disturbances on the structure and biodiversity of boreal forests on acidic soils and created a statistically supported rational set of indicators to monitor the stand “naturalness”. For that, we surveyed various traits of tree layer, understory, herb layer, forest floor and several widely accepted biodiversity epiphytic indicators in 252 old‐aged boreal stands in Estonia, mostly dominated by Scots pine or Norway spruce. Multifactorial general linear model analyses showed that many forest characteristics and potential indicators were confounded by the gradient of soil productivity (reflected by the forest site type), local biogeographic gradients and also by stand age. Considering confounding effects, boreal forests in a near‐natural state have more large‐diameter trees (diameter at breast height >40 cm) and larger variety of diameter classes, higher proportion of spruce or deciduous trees, a larger amount of coarse woody debris in various stages, a more closed tree canopy and denser understory than managed mature forests. By increasing light availability above the field layer, forest management indirectly increases the coverage of herbs and lichens on the forest floor but reduces the alpha‐ and beta‐diversity of herbs and the proportion of graminoids. Human disturbances reduce the relative incidence of many commonly accepted biodiversity indicators such as indicator lichens, woodpeckers, wood‐dwelling insects or fungi on trees. The test for the predictive power of characteristics reacting on disturbance revealed that only a fraction of them appeared to be included in a diagnostic easy‐to‐apply set of indicators to assess the nature quality of boreal forest: the amount of dead wood, the proportion of deciduous trees, the presence of specially shaped trees and woodpeckers and, as an indicator of disturbances, the forest herb Melampyrum pratensis. Many of these indicators have already been implemented in practice. 相似文献
165.
《Journal of enzyme inhibition and medicinal chemistry》2013,28(3):332-340
In this study, a series of novel 1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazole (6a–g) and 1,3,4-oxadiazole (7a–g, 8) were synthesized from N-(6-chlorobenzo[d]thiazol-2-yl) hydrazine carboxamide derivatives of benzothiazole class. Antimicrobial properties of the title compound derivatives were investigated against one Gram (+) bacteria (Staphylococcus aureus), three Gram (?) bacteria (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae) and five fungi (Candida albicans, Aspergillus niger, Aspergillus flavus, Monascus purpureus and Penicillium citrinum) using serial plate dilution method. The investigation of antibacterial and antifungal screening data revealed that all the tested compounds showed moderate to good inhibition at 12.5–100?µg/mL in DMSO. It has been observed that triazolo-thiadiazole derivatives are found to be more active than 1,3,4-oxadiazole derivatives against all pathogenic bacterial and fungal strains. 相似文献
166.
《Journal of enzyme inhibition and medicinal chemistry》2013,28(3):323-330
An ideal anti-inflammatory drug should have the desired effect in minimum dose with minimum side effects. Antimicrobial actions associated with such agents will be an added advantage as they broaden the spectrum of the compounds. Promising anti-inflammatory and antimicrobial activity together with low ulcerogenic properties of some 2(3H)-furanones, synthesized in our previous study, prompted us to investigate the effect of the isobutyl group on their pharmacological profile. Since compounds 3, 9, 13, and 14 have both anti-inflammatory and analgesic effects in addition to low ulcerogenic incidence, they were selected for investigation of their inhibitory effects on various cyclo-oxygenase enzymes. It was found that they were more selective toward COX-2 enzymes. An MIC of 6.25 μg/mL was recorded for compounds 3, 13, and 14 against S. aureus, E. coli, R. oryza, and P. citrum. The study supports the development of furanone derivatives as potential anti-inflammatory agents with antimicrobial activity. 相似文献
167.
《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):84-91
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. 相似文献
168.
《Journal of enzyme inhibition and medicinal chemistry》2013,28(3):495-508
The synthesis of a series of 2,3-diaryl-7-methyl-4,5,6,7-tetrahydroindazole and 3,3a,4,5,6,7-hexahydroindazole derivatives substituted with various biologically-active function groups with anticipated chemotherapeutic activity is described. 4-(7-methyl-3-aryl-3,3a,4,5,6,7-hexahydro-indazol-2-yl)benzenesulfonamides 2a–c, which were employed as key intermediates in this study, were synthesized by cyclocondensation of 6-arylidene-2-methylcyclohexanones 1a–c with 4-hydrazinobenzenesulfonamide hydrochloride. A detailed discussion of the reactions utilized in the preparation of the intermediate and target compounds is reported, and the structures of the newly synthesized compounds were substantiated with IR, 1H and 13C NMR spectral data and elementary microanalyses. Twenty of the newly synthesized compounds were selected by National Cancer Institute (NCI), Maryland, USA, to be evaluated for their antitumor activity and the results revealed that six compounds 3c, 4d,e, 5a,d and 8c exhibited broad spectrum of antitumor activity against most of the tested tumor cell lines. In addition, the in vitro antibacterial and antifungal activities of a number of the target compounds were also tested using the Agar-diffusion method. Some of these compounds have shown significant antibacterial and mild to moderate antifungal activities. 相似文献
169.
《Expert review of proteomics》2013,10(2):137-140
Accurate cancer biomarkers are needed for early detection, disease classification, prediction of therapeutic response and monitoring treatment. While there appears to be no shortage of candidate biomarker proteins, a major bottleneck in the biomarker pipeline continues to be their verification by enzyme linked immunosorbent assays. Multiple reaction monitoring (MRM), also known as selected reaction monitoring, is a targeted mass spectrometry approach to protein quantitation and is emerging to bridge the gap between biomarker discovery and clinical validation. Highly multiplexed MRM assays are readily configured and enable simultaneous verification of large numbers of candidates facilitating the development of biomarker panels which can increase specificity. This review focuses on recent applications of MRM to the analysis of plasma and serum from cancer patients for biomarker verification. The current status of this approach is discussed along with future directions for targeted mass spectrometry in clinical biomarker validation. 相似文献
170.