74 research outputs found
Editorial: Advances in the discovery of natural molecules and their analogues against microbial infection-related biofilms
No full textEditorial on the Research Topic
Advances in the discovery of natural molecules and their analogues
against microbial infection-related biofilm
A Food-Grade Resin with LDH–Salicylate to Extend Mozzarella Cheese Shelf Life
No full textMozzarella cheese can be considered by far the world’s most popular Italian dairy product. Extending the shelf life of mozzarella cheese is an important issue in the dairy industry due to the high risk of contamination by several bacteria species, including spoilage pseudomonads. In this work, active packaging was prepared by coating traditional polyethylene terephthalate (PET) containers of “ovoline” mozzarella cheese with a food-grade resin mixed with a layered double hydroxide (LDH) in which salicylate anion was intercalatedby ionic exchange.. This antimicrobial molecule is listed in EC-Directive 10/2011/EC of 14 January 2011. Morphological arrangement of the molecule into the LDH layers was evaluated by X-ray diffraction (XRD) and controlled release followed by UV spectroscopy. Then, active trays were used to pack the mozzarella cheeses stored for 20 days at 4 °C and under thermal abuse (15 °C). Samples from both conditions showed coliform reduction (by ca. 2 log CFU/g) throughout the storage period. Depending on temperature, total mesophilic aerobic bacteria, Pseudomonas spp., yeasts, and mold loads were reduced in the first 3 days; at 4 °C. Slower acidification and lower proteolysis were also found in treated samples in comparison to control ones. The fitting of the Gompertz function to coliforms and spoilage pseudomonads highlighted an increase in the shelf life of mozzarella cheese of ca. 2 days at 4 °C. These results suggest that salicylate–LDH-coated PET may be applied to extend the shelf-life of mozzarella cheese and also counteract its spoilage if accidental interruptions to refrigeration occur
Antimicrobial and antibiofilm activities of citrus water-extracts obtained by microwave-assisted and conventional methods
No full textCitrus pomace is a huge agro-food industrial waste mostly composed of peels and traditionally used as compost or animal feed. Owing to its high content of compounds beneficial to humans (e.g., flavonoids, phenol-like acids, and terpenoids), citrus waste is increasingly used to produce valuable supplements, fragrance, or antimicrobials. However, such processes require sustainable and efficient extraction strategies by solvent-free techniques for environmentally-friendly good practices. In this work, we evaluated the antimicrobial and antibiofilm activity of water extracts of three citrus peels (orange, lemon, and citron) against ten different sanitary relevant bacteria. Both conventional extraction methods using hot water (HWE) and microwave-assisted extraction (MAE) were used. Even though no extract fully inhibited the growth of the target bacteria, these latter (mostly pseudomonads) showed a significant reduction in biofilm biomass. The most active extracts were obtained from orange and lemon peel by using MAE at 100 °C for 8 min. These results showed that citrus peel water infusions by MAE may reduce biofilm formation possibly enhancing the susceptibility of sanitary-related bacteria to disinfection procedures
Thiol-Activated Anticancer Agents: The State of the Art
No full textThe thiol or sulfhydryl group, as part of low molecular weight non-peptide biomolecules, as well as part of the cysteine residues in peptides and proteins, is known to play extremely important roles in several aspects of cellular function. Glutathione (γ-Glu-Cys-Gly; GSH) is the most abundant thiol-containing peptide in mammals, being present intracellularly in the low millimolar concentration range, but only in the low micromolar concentration range in the majority of extracellular fluids. Notably, intracellular levels of GSH have been found to be significantly upregulated in a number of human cancers, a phenomenon thought to contribute, in concert with overexpression of some GSHassociated enzymes, to the development of tumor cell chemo- and radioresistance. On the other hand, various natural and synthetic chemical entities of different sizes show significant cytotoxic activity only upon interaction with a thiol, and can therefore exploit the GSH-rich intracellular environment of tumors. This review article attempts to summarize the current structural and pharmacological knowledge in the field of thiol-activated anticancer agents, with a focus on the mechanism(s) of their activation. Even though a great part of the available thiol-activated anticancer compounds is still in the preclinical phase of testing, some of them are undergoing trials in cancer patients
Caratterizzazione preclinica in vitro di nuovi inibitori non peptidomimetici della glutatione trasferasi P1-1
No full textGlutathione transferases (formerly glutathione S-transferases, GSTs) are a superfamily of enzymes involved in the glutathione (GSH)-dependend detoxification of a wide range of chemicals, including drugs. Moreover, certain members of this superfamily interact with and modulate the activity of protein kinases involved in key cellular processes, including proliferation and apoptosis [Ruzza et al., 2009]. Among them, GSTP1-1 is frequently overexpressed in a variety of human tumors, where it contributes to conferring resistance to different anticancer agents. In light of these observations, several GST inhibitors or GST-activated prodrugs have been investigated throughout the years; however, none of them has been approved for use as antitumor drug [Ruzza et al., 2009; Sau et al., 2010].
6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) and its structural analogue MC3181 are promising anticancer agents with potent inhibitory activity towards GSTP1-1 [Ricci et al., 2005; Pasello et al., 2011; De Luca et al., 2014]. A first aim of this work was to evaluate the metabolic fate of these compounds in humans and in laboratory animal species. The metabolic stability of NBDHEX and MC3181 was assessed by high performance liquid chromatography (HPLC) or LC coupled to diode array detection and tandem mass spectrometry (LC-DAD-MS/MS), upon incubation of each drug with human, mouse or rat liver microsomes or cytosol as enzyme source. The reactions investigated were UDP-glucuronic acid (UDPGA)-dependent glucuronidation, reduced nicotinamide adenine dinucleotide phosphate (NADPH)-dependent microsomal oxidation, and oxidized nicotinamide adenine dinucleotide (NAD+)-dependent cytosolic oxidation.
Both NBDHEX and MC3181 underwent glucuronidation and microsomal NADPH-dependent oxidation in all of the investigated species. Moreover, NBDHEX, but not MC3181, underwent alcohol dehydrogenase-dependent oxidation in both human, rat and mouse cytosol.
The identity of NBDHEX glucuronide was confirmed by nuclear magnetic resonance analyses.
Finally, interspecies differences were identified in the glucuronidation of both compounds and in the cytosolic oxidation of NBDHEX, while sex-related differences were observed in the rate of glucuronidation of MC3181 as well as in the rate of cytosolic oxidation of NBDHEX.
Sulfasalazine (sulfasalazopyridine; SASP), a drug currently used to treat rheumatic and inflammatory bowel diseases, is a non-substrate inhibitor of various human GSTs, including GSTP1-1 [Ahmad et al., 1992]. Despite this, its poor oral bioavailability and metabolic instability (which is mainly linked to the presence of an azo group in its structure) hinder its use as an anticancer agent. In this work, 30 SASP analogues containing an imidazole ring in substitution of the azo group of SASP (i.e. salycylbenzoimidazole derivatives, EML), have been investigated as potential inhibitors of human GSTP1-1. Further structural modifications involved the sulfonamide as well as the aminosalicylic moiety of the drug.
Seven out of 30 of the salycylbenzoimidazole derivatives studied (i.e. EML340, EML277, EML259, EML337, EML357, EML279, and EML338) inhibited human placental GST (mostly GSTP1-1) conjugation activity more efficiently than the parent compound, SASP. Thus, the azo group seems to be not essential for inhibition of the enzyme activity.
Further enzyme inhibition assays carried out using human recombinant GST A1-1, M1-1 and P1-1, showed that EML337 displays a certain grade of selectivity for GSTP1-1, while EML340 and EML277 were highly selective towards GSTM1-1.
Finally, preliminary in vitro cytotoxicity assays indicate that the methyl esters EML259, EML337 and EML339 can interfere with the growth of A375 and SK-MEL 23 human melanoma cell lines
Proteome response of Staphylococcus xylosus DSM 20266T to anaerobiosis and nitrite exposure
No full textThe viability and competitiveness of Staphylococcus xylosus in meat mostly depend on the ability to adapt itself to rapid oxygen and nutrients depletion during meat fermentation. The utilization of nitrite instead of oxygen becomes a successful strategy for this strain to improve its performance in anaerobiosis; however, metabolic pathways of this strain underlying this adaptation, are partially known. The aim of this study was to provide an overview on proteomic changes of S. xylosus DSM 20266T cultured under anaerobiosis and nitrite exposure. Thus, two different cultures of this strain, supplemented or not with nitrite, were in vitro incubated in aerobiosis and anaerobiosis monitoring cell viability, pH, oxidation reduction potential and nitrite content. Protein extracts, obtained from cells, collected as nitrite content was depleted, were analyzed by 2DE/MALDI-TOF/TOF-MS. Results showed that DSM 20266T growth was significantly sustained by nitrite in anaerobiosis, whereas no differences were found in aerobiosis. Accordingly, nitrite content was depleted after 13 h only in anaerobiosis. At this time of sampling, a comparative proteomic analysis showed 45 differentially expressed proteins. Most differences were found between aerobic and anaerobic cultures without nitrite; the induction of glycolytic enzymes and glyoxylate cycle, the reduction of TCA enzymes, and acetate fermentation were found in anaerobiosis to produce ATP and maintain the cell redox balance. In anaerobic cultures the nitrite supplementation partially restored TCA cycle, and reduced the amount of glycolytic enzymes. These results were confirmed by phenotypic microarray that, for the first time, was carried out on cell previously adapted at the different growth conditions. Overall, metabolic changes were similar between aerobiosis and anaerobiosis NO2-adapted cells, whilst cells grown under anaerobiosis showed different assimilation profiles by confirming proteomic data; indeed, these latter extensively assimilated substrates addressed at both supplying glucose for glycolysis or fueling alternative pathways to TCA cycle. In conclusion, metabolic pathways underlying the ability of S. xylosus to adapt itself to oxygen starvation were revealed; the addition of nitrite allowed S. xylosus to take advantage of nitrite to this condition, restoring some metabolic pathway underlying aerobic behavior of the strain
Positional isomers of mannose-quinoline conjugates and their copper complexes: Exploring the biological activity
No full text8-Hydroxyquinolines show a wide range of pharmacological activities, and some are marketed as therapeutic agents. Despite the significant number of biologically active hydroxyquinolines proposed, there is a continued interest in the development of new active derivatives to overcome the drawbacks associated with their use. Herein, we report the synthesis and characterization of a set of positional isomers of hydroxyquinoline-mannose conjugates. Since in many cases the complexation ability of 8-hydroxyquinolines seems to be responsible for their pharmacological activities, we investigated the capacity of these systems to complex copper(ii) ions. We also examined diverse biological activities (antiproliferative, antimicrobial and antioxidant) of the new derivatives and their copper(ii) complex and compared them to those of their parent compounds and an analogous glucose-quinoline conjugate. All compounds show antioxidant activity that depends on the regioisomer. Moreover, specific isomers show significant antibacterial activity against P. aeruginosa and S. aureus. Furthermore only a regioisomer shows a pharmacologically relevant antiproliferative activity against human tumor cells, in the presence of copper(ii) ions
Alternative Protein Sources and Novel Foods: Benefits, Food Applications and Safety Issues
No full textThe increasing size of the human population and the shortage of highly valuable proteinaceous ingredients has prompted the international community to scout for new, sustainable, and natural protein resources from invertebrates (e.g., insects) and underutilized legume crops, unexploited terrestrial and aquatic weeds, and fungi. Insect proteins are known for their nutritional value, being rich in proteins with a good balance of essential amino acids and being a valuable source of essential fatty acids and trace elements. Unconventional legume crops were found rich in nutritional, phytochemical, and therapeutic properties, showing excellent abilities to survive extreme environmental conditions. This review evaluates the recent state of underutilized legume crops, aquatic weeds, fungi, and insects intended as alternative protein sources, from ingredient production to their incorporation in food products, including their food formulations and the functional characteristics of alternative plant-based proteins and edible insect proteins as novel foods. Emphasis is also placed on safety issues due to the presence of anti-nutritional factors and allergenic proteins in insects and/or underutilized legumes. The functional and biological activities of protein hydrolysates from different protein sources are reviewed, along with bioactive peptides displaying antihypertensive, antioxidant, antidiabetic, and/or antimicrobial activity. Due to the healthy properties of these foods for the high abundance of bioactive peptides and phytochemicals, more consumers are expected to turn to vegetarianism or veganism in the future, and the increasing demand for such products will be a challenge for the future
Initial characterization of the metabolic stability of the selective and potent glutathione transferase P1-1 inhibitor 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) in liver microsomes and cytosol: an interspecies comparison
No full textInitial in vitro interspecies comparison of hepatic metabolism of the investigational anticancer agent 6-(7-nitro-2,1,3-benzoxadiazol-4- ylthio)hexanol (NBDHEX)
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