Molecular Dynamics studies on Mdm2 complexes: an analysis of the inhibitor influence

p53 is a powerful anti-tumoral molecule frequently inactivated by mutations or deletions in cancer. However, half of all human tumors expresses wild-type p53, and its activation, by antagonizing its negative regulator Mdm2, might offer a new strategy for therapeutic protocol. In this work, we present a molecular dynamics study on Mdm2 structure bound to two different known inhibitors with the aim to investigate the structural transitions between apo-Mdm2 and Mdm2-inhibitor complexes. We tried to gain information about conformational changes binding a benzodiazepine derivative inhibitor with respect the known nutlin and the apo form. The conformational changes alter the size of the cleft and were mainly in the linker regions, suggesting that the overall dynamic nature of Mdm2 is related to dynamic movements in these regions

Pharmacophore modelling as useful tool in the lead compounds identification and optimization

The goal of computer-aided molecular design methods in modern medicinal chemistry is to reduce the overall cost and time associated to the discovery and development of a new drug by identifying the most promising candidates to focus the experimental efforts on. Very often, many drug discovery projects have reached already a well-advanced stage before detailed structural data on the protein target have become available. A possible consequence is that often, medicinal chemists develop novel compounds for a target using preliminary structure–activity information, together with the theoretical models of interactions. Only responses that are consistent with the working hypothesis contribute to an evolution of the used models. Within this framework, the pharmacophore approach has proven to be successful, allowing the perception and understanding of key interactions between a receptor and a ligand[1]. In recent years, our research group exploited this useful modeling tool with the aim to identify new chemical entities and/or optimizing known lead compounds to obtain more active drugs in the field of antitumor, antiviral, and antibacterial drugs. In this communication, we present an overview of our recent works in which we used the pharmacophore modelling approach combined with induced fit docking, 3D-QSAR approach, and HTVS for the analysis of drug-receptor interactions and the discovery of new inhibitors of IKKβ, Bcl-xl, and c-kit tyrosine kinase, all targets involved into the initiation and the development of different types of cancer[2-5]

First report on the presence of Alloxan in Bleached Flour by LC-MS/MS

n/

Evaluation of Histamine level in the Red Tuna (Thunnus thynnus) of the Mediterranean Sea in 2010–2015

n/

The cold chain and the COVID-19 pandemic: an unusual increase in histamine content in fish samples collected in Southern Italy during lockdown

Objectives We analysed 900 samples of fresh (250) and processed (650) fish products collected in Sicily (Southern Italy) in 2020 during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic (hereafter: COVID-19). Materials and methods The samples were divided temporally based on five phases relating to the various restrictions imposed by the Italian government in this period. The validated method of ultra-high performance liquid chromatography (UHPLC) combined with a diode array detector (DAD) was then employed for the analysis. Results The samples collected during the Phase I lockdown period and after it had ended (Phase II) revealed significant increases in the mean histamine levels: 41.89±87.58 mg/kg -1 and 24.91±76.76 mg/kg -1, respectively. The 11 (1.3% of the total) fresh fish samples that were identified as being non-compliant with EC Reg. 2073/2005 were only found during these two periods. All the processed samples were always compliant. The histamine values decreased as the restrictions eased, achieving a mean value of 11.16±9.3 mgkg -1 (Phase III). Conclusions There was an increase in the incidence of fish samples that were non-compliant with EC Reg. 2073/2005 compared to previous surveillance data. These results provide a first report on the effect of lockdown measures on food safety and the cold chain. Our findings must cause food safety operators to intensify their controls over fresh fish products in such periods to safeguard consumer health. Further studies are required to evaluate whether the same trend would be observed with other food contaminants

Polyphenols of white lupin (Lupinus albus L.) seeds cultivated in Southern Italy by a LC-HRMS method

: In this work we examined the contents of 14 polyphenols in white lupin (Lupinus albus L.) samples cultivated in Southern Italy by the optimisation and validation of a LC-HRMS method. The validation of the LC-HRMS method showed linearity results r2 > 0.989 and recovery values between 71 and 119% for a very wide range of concentrations. Ellagic acid was the most abundant polyphenol, with mean concentrations of 16271.86 ± 19798.53 μg/Kg, followed by apigenin (2749.51 ± 889.95 μg/Kg). A significant variability in ellagic acid contents was found between the areas of cultivation examined (p < 0.05). As far as we know, this work provides the first data on the polyphenols contents of white lupins cultivated in Italy. The comparison with other study confirms the role of the cultivation area for the determination of the polyphenol's contents. The study also confirms white lupins as a promising source of antioxidant and anti-inflammatory substances in a balanced diet

Toxic metals in Loggerhead sea turtles (Caretta caretta) stranded freshly dead along Sicilian coasts

Abstract Background: The Loggerhead sea turtle (Caretta caretta) is a marine reptile belonging to a monophyletic group of chelonians. As these animals are long-lived, they have the ability to accumulate pollutants. Aim: To collect epidemiological data on toxic metals in marine Loggerhead sea turtles. Materials and Methods: Forty Loggerhead sea turtles comprising 25 males and 15 females stranded freshly dead between 2013 and 2018 along the coasts of Sicily, Southern Italy, were examined for arsenic, cadmium, and lead accumulation in muscle and adipose tissues by means of a validated ICP-MS method. A modified K index as a growth condition factor, namely Fulton's K index, was used. Samples were tested in duplicate. A Wilcoxon rank sum test was carried out to evaluate metal contents differences between muscle and adipose tissues and between genders. Results: The Fulton's K index suggested a good body condition of the C. caretta recovered with mean values of 5.34±3.40 (n=40; ±SD). Detectable concentrations of lead were found in 70% of the samples analysed with mean values of 0.65±1.67 mg/kg wet weight and 0.51±1.29 mg/kg wet weight in muscle and adipose tissues, respectively. No significant differences in arsenic, cadmium, and lead were detected between genders. In addition, no significant correlation was found between modified K index and concentrations of arsenic, cadmium, and lead. Clinical relevance: Findings on muscle and adipose tissues suggest chronic exposure of Caretta caretta to high concentrations of especially lead which might negatively affect health and welfare of these marine turtles although body condition was good

Salmo salar fish waste oil: Fatty acids composition and antibacterial activity

Background and aims Fish by-products are generally used to produce fishmeal or fertilizers, with fish oil as a by-product. Despite their importance, fish wastes are still poorly explored and characterized and more studies are needed to reveal their potentiality. The goal of the present study was to qualitatively characterize and investigate the antimicrobial effects of the fish oil extracted from Salmo salar waste samples and to evaluate the potential use of these compounds for treating pathogen infections. Methods Salmo salar waste samples were divided in two groups: heads and soft tissues. Fatty acids composition, and in particular the content in saturated (SAFAs), mono-unsaturated (MUFAs) and Polyunsaturated (PUFAs) fatty acids, was characterized through GC/MS Thermo Focus GC-DSQ II equipped with a ZB-5 fused silica capillary tubes column. The antimicrobial activity of the salmon waste oils was evaluated through the Minimum Inhibitory Concentration assay and the antibiotics contamination was determined by Liquid Chromatography with tandem Mass Spectrometry (LC-MS/MS) analysis. All experiments were done at least in triplicate. Results GC/MS analysis has shown the specific fatty acid composition of the salmon waste oils and their enrichment in MUFAs and PUFAs, with special reference to omega-3, -6, -7, -9 fatty acids. Furthermore, our study has highlighted the antimicrobial activity of the fish waste oil samples against two Gram+ and Gram- bacterial strains. Conclusions These data confirm that the fish waste is still quantitatively and qualitatively an important source of available biological properties that could be extracted and utilized representing an important strategy to counteract infective diseases in the context of the circular economy