Search

The study aimed to identify the mixtures of natural products to be added to the drippers (used in drip irrigation) during their preparation, so that the slow release of phytotoxic substances with the passage of water reduces or eliminates the intrusion of roots in the drippers. In field studies, we selected five phytotoxic plant species [Vetch villosa Roth., Brassica juncea L., Secale cereale L., Juncus effusus L. and Vallisneria natans L.] and their hydroalcoholic extracts were tested on two dicotyledons [Lactuca sativa L. cv Cavolo di Napoli and Lycopersicon esculentum L.] and one monocotyledon, Allium cepa L. We determined the structure of the main components of each extract. The Vetch villosa extract was most inhibitory. Further studies are required to determine whether to use the extract as such or one or more of its individual components can be used as possible additive in subsurface irrigation drip.

In the literature there are hundreds of articles, the first dating back to 1866 and the last to 2014, on gymnemic acid, isolated from Gy mnema sylvestre, from its isolation to the determination of its biological activities. Gymnemic acid has a CAS number but its structure is not specified. Studies during the second half of the 1970s clearly demonstrated that what was being referred to as gymnemic acid is actually a very complex mixture of dozens of substances, belonging to different classes of natural compounds. This plant, whose infusions or complex mixtures of its metabolites are the basis for many formulas sold in pharmacies and by herbalists, has anti-diabetic and slimming effects. It is certainly misleading to talk about gymnemic acid as a specific molecule. There may be doubts about the exact composition of the products, and consequently about their origin and the claimed effects.

A new and versatile on-line automated solid-phase approach to obtain cyclic PNA (I and III) and cyclic PNA-DNA chimeras (II) in highly pure form has been developed. Starting from a Tentagel matrix functionalized with a 3-chloro-4-hydroxyphenylacetic linker, the synthesis of representative, new cyclic molecules by standard peptide and phosphoramidite-based chemistry has been achieved. © 2006 American Chemical Society.

Two new thymidine based polymeric supports, in which the nucleosides have been anchored through the thymine moiety to a β-hydroxy thioether functionalized resin via a Mitsunobu reaction, have been prepared. A simple and efficient solid-phase synthesis of 5′,3′-bis-derivatized thymidine analogues has so been developed, following methodologies well established in peptide and oligonucleotide chemistry and is here proposed for the preparation of a variety of different nucleoside conjugate products. © 2001 The Royal Society of Chemistry.

York (Regno Unito)

Gluco- and ribosylation of the bases of sugar protected inosine and uridine were investigated, obtaining only adducts with beta -configuration at thenew glycosidic carbon; stereospecific insertion of a sugar moiety at the 1-N of inosine was achieved either using a Mitsunobu approach (for ribosylation) or by direct coupling of 1-alpha -bromoglucose 13 with 2',3',5'-tri-O-acetylinosine for glucosylation. 1-(beta -D-glucosyl)-inosine, chosen as starting substrate for glucosylated analogs of cyclic IDP-ribose, was phosphorylated at the primary hydroxyls and tested in intramolecular pyrophosphatebond formation.

A convenient solid-phase synthesis of oligonucleotides conjugated at the 3'-end with a tetraphenylporphyrin residue, by means of a new polymeric support bearing as a linker a lysine derivative, has been developed. A porphyrin linked 17-mer, designed for antisense experiments, has been prepared in good yields, and its hybridization properties with a complementary DNA fragment evaluated by UV thermal analysis.

The aim of our study was to verify the impact of work risk factor in causing cutaneous neoplasia on a group of patients and to assess the risk of exposure to UV on outdoor workers. The survey was divided in three phases: a) Questionnaire, b) Dermatological clinical examination. c) Exposure measurement by spectral radiance method (mW/cm2). 248 subjects were enrolled, 100 of which affected by basal cellular carcinoma (BCC) (68% M and 32% F: mean age 70 +/- 11.93 y) 130 by melanoma (42% M and 58% F; mean age 53 +/- 17.35 y) and 18 by squamous cellular carcinoma (33% F and 67% M: mean age 78 +/- 11.41 y). In addiction 22 healthy male subjects exposed to UV were examined (mean age 38.59 +/- 13.65 y; specific working age 11.88 +/- 10.92 y). The assessment of UV exposure was performed over a 24 days timeframe during summer 2007, all over the working day. Furthermore, maximum allowed exposure time (t(max)) without protection was calculated according to ACGIH guidelines in order to prevent cutaneous alterations. It turned out that the UV exposure, both in working and spare time, is the root cause for squamous cellular cancer developing. Furthermore our results proved that also BCC is related to the overall UV exposure. No clear link to the UV exposure was found for cutaneous melanoma. No precancerous lesions were observed on shortly exposed subjects. The measurements performed revealed, as expected, lower exposure during first and last hours of the day without any particular constrain on t(max), and maximum exposure in the timeframe between 10:00 AM and 4:00 PM. Therefore, it is necessary to pay higher attention to the UV exposure and related consequences on employees health in order to provide with the most suitable preventing measures such the usage of protections depending from the requested exposure time.

The solid-phase synthesis of 3'-derivatized oligonucleotides, by using a support which links the first nucleoside-3'-phosphate through the nucleobase, is reported. Following this procedure, the marking molecules can easily incorporated in satisfactory yields at the 3'-phosphate terminus either before or after the chain assembly.

[reaction: see text] An easy and efficient solid-phase strategy to obtain 5'- and 3'-oligonucleotide conjugates in highly pure form has been developed. Ad hoc derivatized solid supports, to which the first nucleoside unit can be attached through a phosphate linkage, have been exploited both in a pre- and post-DNA assembly conjugation approach. A number of 5'- or 3'- oligonucleotide conjugates, incorporating a variety of labels covalently linked through a phosphodiester or a phosphoramidate bond, have been synthesized and characterized.

Two new thymidine based polymeric supports, in which the nucleosides have been anchored through the thymine moiety to a β-hydroxy thioether functionalized resin via a Mitsunobu reaction, have been prepared. A simple and efficient solid-phase synthesis of 5′,3′-bis-derivatized thymidine analogues has so been developed, following methodologies well established in peptide and oligonucleotide chemistry and is here proposed for the preparation of a variety of different nucleoside conjugate products.

Silybin is the main component of silymarin with antioxidant, anti-inflammatory and cytoprotective actions. Our aim was to compare the effect of silybin used as single substance, silybin-phosphatidylcholine complex (SilPho), and derivatives of silybin (MannpSil, GalpSil, GlcpSil, LactpSil) on MKN28 and HepG2 cell viability and cell death, in vitro, after induction of oxidative stress.

Background. Sepsis is the major cause of mortality from any infectious disease worldwide. Sepsis may be the result of a healthcare associated infection (HAI): the most frequent adverse events during care delivery especially in Intensive Care Units (ICUs). The main aim of the present study was to describe the epidemiology of ICU-acquired sepsis and related outcomes among patients enrolled in the framework of the Italian Nosocomial Infections Surveillance in ICUs - SPIN-UTI project. Study design. Prospective multicenter study. Methods. The SPIN-UTI network adopted the European protocols for patient-based HAI surveillance. Results. During the five editions of the SPIN-UTI project, from 2008 to 2017, 47.0% of HAIs has led to sepsis in 832 patients. Overall, 57.0% episodes were classified as sepsis, 20.5% as severe sepsis and 22.5% as septic shock. The most common isolated microorganisms from sepsis episodes were Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa. The case fatality rate increased with the severity of sepsis and the mean length of ICU-stay was significantly higher in patients with ICU-acquired sepsis than in patients without. Conclusions. Our study provides evidence that ICU-acquired sepsis occurs frequently in Italian ICU patients and is associated with a high case fatality rate and increased length of stay. However, in order to explain these findings further analyses are needed in this population of ICU patients.

Background and aim: Silybin is the main component of Silymarin with an increasing number of documented effects. The main effects attributed both in vitro and in vivo to Silybin are related to its antioxidant, antiinflammatory and cytoprotective actions. This study was designed to compare, in vitro, the effect of Silybin used as single substance, Silybin–phosphatidylcholine complex (SilPho), and derivatives of Silibinin (MpSil, GpSil, GlpSil, LipSil) on MKN28 and HepG2 cell viability and cell death after the induction of oxidative stress. Material and methods: Oxidative stress was induced by incubating HepG2 and MKN28 cells with xanthine oxidase in the presence of its substrate xanthine for periods of up to three hours. Cell viability was determined by the MTT assay. We evaluated whether X-XO increased cellular MDA, a marker of lipid peroxidation, and whether Silybin and SilPho pretreatment was able to counteract any such effect. Results: In basal conditions, the pre-incubation of MKN28 and HepG2 cells with Silybin, SilPho, and new Silibinin glycoconjugates lead to two different results. In fact, SilPho and new Silibinin glycoconjugates don’t affect cell viability, while Silybin induced a cell death of about 50%, also at the lower dose used, both in MKN28 and in HepG2 cells. The pre-incubation with Silybin and new Silibinin glycoconjugates don’t affect cell viability, while SilPho shows a protective effect. Exposure of MKN28 cells to X-XO caused a twofold increase in cellular MDA concentration compared with control untreated cells. Moreover, pretreatment with SilPho but not with Silybin significantly prevented X-XO induced increase in cellular MDA. Conclusions: This suggests that the protective effect of SilPho is partially due to inhibition of ROS induced lipid peroxidation.

Alzheimer's disease (AD) is a multifactorial pathology that requires multifaceted agents able to address its peculiar nature. Increasing evidence has shown that aggregation of amyloid β (Aβ) and oxidative stress are strictly interconnected, and their modulation might have a positive and synergic effect in contrasting AD-related impairments. Herein, a new and efficient fragment-based approach towards tyrosol phosphodiester derivatives (TPDs) has been developed starting from suitable tyrosol building blocks and exploiting the well-established phosphoramidite chemistry. The antioxidant activity of new TPDs has been tested as well as their ability to inhibit Aβ protein aggregation. In addition, their metal chelating ability has been evaluated as a possible strategy to develop new natural-based entities for the prevention or therapy of AD. Interestingly, TPDs containing a catechol moiety have demonstrated highly promising activity in inhibiting the aggregation of Aβ40 and a strong ability to chelate biometals such as CuII and ZnII .

Octocrylene is an organic sunscreen whose main action is to absorb UVB radiation and short UVA wavelengths; it is used in various cosmetic products in order to provide an adequate sun-protection factor or to protect the cosmetic formulations themselves from UV radiation. This filter is believed to be a possible endocrine disruptor and is also questioned due to its allergic and/or photoallergic potential. However, it continues to be widely used, and it has been found in various environments, not least those of swimming pools, where it is evidently released by consumers, to the point that it is now considered an emerging micropollutant. The present investigation presents the possible chemical fate of octocrylene in the typical chlorination conditions of wastewater or swimming pools. A total of 11 disinfection byproducts were identified, and 6 were identified for the first time, and separated by HPLC. These products were identified through careful mass spectrometry studies and 1D and 2D NMR experiments. A formation mechanism has been proposed that justifies the chemical structures of all of the compounds identified. The ecotoxicological assessment of octocrylene and their products was carried out by employing Phaeodactylum tricornutum, Brachionus plicatilis and Aliivibrio fischeri as bioindicators. The ecotoxicity results reveal that toxic byproducts might be generated during the oxidation process, increasing the potential risk to the marine environment.

Oligonucleotides carrying a peptide nucleic acid (PNA) tail at the 3′-end have been efficiently prepared by an on-line automated synthetic protocol exploiting commercially available Bhoc/Fmoc PNA monomers for the assembly of the PNA tract, followed by a deprotection/reprotection of the base protecting groups. The syntheses of the ODN domain in the chimeras have then been performed by standard methods. The hybridization properties of the synthesized chimeras with complementary DNA fragments have been investigated by thermal denaturation experiments. © 2001 Elsevier Science Ltd. All rights reserved.

Antihypertensive drugs are among the most prescribed drugs. Olmesartan acid, of the sartan class, belongs to a relatively new generation of antihypertensive drugs called angiotensin II receptor blockers. There are very few studies on the presence and fate of sartans in the environment, despite them being marketed in huge quantities, metabolized in low percentages, and detected in wastewater and water bodies. This paper presents a study on the less abundant and more polar fractions that have been neglected in previous studies, which led to the isolation by chromatographic methods of thirteen degradation byproducts (DPs), six of which are new, identified by nuclear magnetic resonance and mass spectrometry. A mechanism of degradation from the parent drug was proposed. The ecotoxicity of olmesartan acid and identified compounds was evaluated in Aliivibrio fischeri bacteria and Raphidocelis subcapitata algae to assess acute and chronic toxicity. For 75% of the DPs, acute and chronic exposure to the compounds, at concentrations of 5 mg/L, inhibited population growth in the algae and decreased bioluminescence in the bacteria.

Curcumin is a bioactive natural compound with a wide range of pharmacological properties, including antitumor activity; however, its clinical application has been limited because of its low solubility, stability, and bioavailability. In this study, a solid phase approach was proposed for the combinatorial synthesis of a mini library of the mimics of curcumin in good purity and yield. The non-effective findings in pancreatic cancer cells switched to strong growth inhibition and cell death efficacy for PC3 prostate cancer cells, and mimic 9, in which tyrosol (TYR) and homovanillyl alcohol (HVA) units were linked by a phosphodiester bond, was quite effective not only in cell growth inhibition but also in causing strong cell death under the study conditions and treatments that were not effective in PANC1 cells. The results got more exciting when we also consider the findings in SW480 human colorectal carcinoma cell line, where the growth inhibitor effects were more in line with that of the PC3 cells, but the lack of cell death effect was more in line with the PANC1 cells.

Type 2 Diabetes is a major public health threat, and its prevalence is increasing worldwide. The abnormal accumulation of islet amyloid polypeptide (IAPP) in pancreatic β-cells is associated with the onset of the disease. Therefore, the design of small molecules able to inhibit IAPP aggregation represents a promising strategy in the development of new therapies. Here we employ in vitro, biophysical, and computational methods to inspect the ability of Silybin A and Silybin B, two natural diastereoisomers extracted from milk thistle, to interfere with the toxic self-assembly of human IAPP (hIAPP). We show that Silybin B inhibits amyloid aggregation and protects INS-1 cells from hIAPP toxicity more than Silybin A. Molecular dynamics simulations revealed that the higher efficiency of Silybin B is ascribable to its interactions with precise hIAPP regions that are notoriously involved in hIAPP self-assembly i.e., the S20-S29 amyloidogenic core, H18, the N-terminal domain, and N35. These results highlight the importance of stereospecific ligand-peptide interactions in regulating amyloid aggregation and provide a blueprint for future studies aimed at designing Silybin derivatives with enhanced drug-like properties.

Silibinin is the main biologically active component of silymarin extract and consists of a mixture 1:1 of two diastereoisomeric flavonolignans, namely silybin A (1a) and silybin B (1b), which we call here silybins. Despite the high interest in the activity of this flavonolignan, there are still few studies that give due attention to the role of its stereochemistry and, there is still today a strong need to investigate in this area. In this regard, here we report a study concerning the radical scavenger ability and the antiproliferative activity on different cell lines, both of silybins and phosphodiester-linked silybin dimers. An efficient synthetic strategy to obtain silybin dimers in an optical pure form (6aa, 6ab and 6bb) starting from a suitable building block of silybin A and silybin B, obtained by us from natural extract silibinin, was proposed. New dimers show strong antioxidant properties, determined through hydroxyl radical (HO●) scavenging ability, comparable to the value reported for known potent antioxidants such as quercetin. A preliminary screening was performed by treating cells with 10 and 50 μM concentrations for 48 h to identify the most sensitive cell lines. The results show that silibinin compounds were active on Jurkat, A375, WM266, and HeLa, but at the tested concentrations, they did not interfere with the growth of PANC, MCF-7, HDF or U87. In particular, both monomers (1a and 1b) and dimers (6aa, 6ab and 6bb) present selective anti-proliferative activity towards leukemia cells in the mid-micromolar range and are poorly active on normal cells. They exhibit different mechanisms of action in fact all the cells treated with the 1a and 1b go completely into apoptosis, whereas only part of the cells treated with 6aa and 6ab were found to be in apoptosis.

The abnormal deposition of Aβ amyloid deposits in the brain is a hallmark of Alzheimer's disease (AD). Based on this evidence, many current therapeutic approaches focus on the development of small molecules halting Aβ aggregation. However, due to the temporary and elusive structures of amyloid assemblies, the rational design of aggregation inhibitors remains a challenging task. Here we combine ThT assays and MD simulations to study Aβ aggregation in the presence of the natural compounds tyrosol (TY), 3-hydroxytyrosol (HDT), and 3-methoxytyrosol (homovanillyl alcohol - HVA). We show that albeit HDT is a potent inhibitor of amyloid growth, TY and HVA catalyze fibril formation. An inspection of MD simulations trajectories revealed that the different effects of these three molecules on Aβ1-40 aggregation are ascribable to their capacity to arrange H-bonds network between the ligand (position C-3) and the peptide (Glu22). We believe that our results may contribute to the design of more effective and safe small molecules able to contrast pathogenic amyloid aggregation.

Numerous substances from different chemical sectors, from the pharmaceutical industry to the many consumer products available for everyday usage, can find their way into water intended for human consumption and wastewater, and can have adverse effects on the environment and human health. Thus, the disinfection process is an essential stage in water and wastewater treatment plants to destroy pathogenic microorganisms but it can form degradation byproducts. Sodium hypochlorite is the most common disinfectant, but the most important drawback associated with this kind of compound is the generation of toxic disinfection byproducts. Many studies have been carried out to identify alternative disinfectants, and in the last few years, peracetic acid has been highlighted as a feasible solution, particularly in wastewater treatment. This study compares the transformations of five emerging pollutants (caffeine, tramadol, irbesartan, diclofenac, trazodone) treated with peracetic acid, to evaluate their degradation and the possible formation of byproducts with those obtained with sodium hypochlorite. Although peracetic acid has many advantages, including a wide field of use against microorganisms and a low toxicity towards animal and plant organisms, it is not as effective in the degradation of the considered pollutants. These ones are recovered substantially and are unchanged quantitatively, producing a very low number of byproducts.

Recently, many studies highlighted the consistent finding of irbesartan in effluents from wastewater treatment plants (WWTPs) and in some rivers and lakes in both Europe and North America, suggesting that no N80% can be removed by specific treatments. The present investigation attempts to study the chemical fate of irbesartan in a simulated chlorination step, mimicking the conditions of a WWTP. A total of six disinfection by-products were identified, five were completely new, and separated on a C-18 column by employing a gradient HPLC method. Initially, a complete mass fragmentation pathway of the drug was established with the help of MS/ TOF, and subsequently, the disinfection by-products were subjected to MS/TOF mass studies to obtain their mass and fragment pattern. The MS results helped to assign tentative structures to the disinfection products, which were verified through 1D and 2D NMR experiments. The chemical structures of the new compounds have been justified by a proposed mechanism of formation. A preliminary ecotoxicity assessment with the crus- tacean Daphnia magna showed that some of the identified by-products were up to 12-times more toxic than irbesartan.