We report the synthesis and in vitro evaluation of novel beta-sheet breaker peptides as promising Aβ fibrillogenesis inhibitors. Further 3D-GRID pharmacophore and metadynamics simulations rationalized the design of these peptides.

Selenosugars are gaining growing interest due to their antioxidant efficacy, and their ability to inhibit glycosidases, repair skin tissue or reduce endothelial dysfunction. Among selenosugars, those in which selenium replaces heterocyclic oxygen in a 5-membered sugar were our focus, and their coupling with phenolic compounds appears to be a strategy aimed at producing new compounds with enhanced antioxidant efficacy. In this context, the Mitsunobu reaction has been advantageously explored to obtain trans-p-coumaroyl-1,4-deoxy-2,3-O-isopropylidene-4-seleno-d-ribose, trans-caffeoyl-1,4-deoxy-2,3-O-isopropylidene-4-seleno-d-ribose, and trans-feruloyl-1,4-deoxy-2,3-O-isopropylidene-4-seleno-d-ribose. These compounds underwent removal of the iso-propylidene group, to provide the corresponding hydroxycinnamoyl-1,4-deoxy-4-seleno-d-ribose. All compounds were characterized by Nuclear Magnetic Resonance (NMR) spectroscopy and High-Resolution Mass Spectrometry (HRMS). This latter technique was pivotal for ensuing cellular metabolomics analyses. In fact, after evaluating the anti-radical efficacy through 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) methods, which underline the massive role of the phenolic moiety in establishing efficacy, the compounds, whose cytotoxicity was first screened in two highly oxidative-stress-sensitive cells, were tested for their wound healing properties towards human HaCaT keratinocytes cells. Caffeoyl- and feruloyl selenosugars exerted a dose-dependent repair activity, while, as highlighted by the metabolomic approach, they were poorly taken up within the cells.

A simple and efficient route for the synthesis of new glycoconjugates has been developed. The approach acts as a model for a mini-library of compounds with a deoxy-selenosugar core joined to a polyphenolic moiety with well-known antioxidant properties. An unexpected stereocontrol detected in the Mitsunobu key reaction led to the most attractive product showing a natural d-configuration. Thus, we were able to obtain the target molecules from the commercially available d-ribose via a shorter and convenient sequence of reactions.

In the last 20 years the exploitation of antioxidant activity of selenobased compounds has improved, just due to the use of Ebselen, a selenocompound, as a Glutathione peroxidase (GPx) mimic. However, their clinical use seems to be compromised by the low solubility in water. To deal with this problem, it is possible to take advantage of the new approach including selenosugars in which selenium replaces heterocyclic oxygen. In this frame, to optimize the antioxidant properties of selenosugars, the glycoconjugation with a polyphenolic unit, which is a molecule capable of inhibiting or disabling the action of free radicals, has been considered in this work. The Mitsunobu reaction mechanism links covalently the primary alcoholic function of selenobased glycosyl donors, coming from the commercially available d‐mannose, and phenolic moiety acceptors, to obtain the corresponding glycoconjugates, has been exploited affording the products in efficient yields. A density functional theory (DFT) theoretical study is carried out to help understand the possible influence of the seleno donor on the reactivity. Crucially, a new pathway based on Pummerer‐like rearrangement followed by a glycosylation, gave a selenosugar with selenium in the ring and bearing an acetal‐like functional group at C‐1. All compounds are characterized by nuclear magnetic resonance (NMR) spectroscopy confirming their structures and purity.

Recent studies have highlighted the potential of plant-based and agro-industrial by-products as valuable sources of bioactive compounds for animal feed formulation. This study aims to evaluate the impact of dietary supplementation with Olea europaea L. leaf extract on the fatty acid composition of pig muscle. Thirty commercial hybrid pigs (Large White × (Landrace × Duroc)), with an initial body weight of 169 ± 7.90 kg and an average age of 10 ± 1 months, were randomly assigned to two experimental groups (n = 15 per group): one fed a standard diet containing Sulla (C) and the other receiving the same diet enriched with olive leaf extract (OL). Over 90 days, the OL group was supplemented with 300 mg/head/day of olive leaf extract, primarily containing oleuropein diglucoside, luteolin-7-glucoside, and verbascoside. The phenolic content, antioxidant activity, bioactive compounds, and fatty acid profiles of both meats and diets were analyzed. Results showed that OL supplementation did not significantly affect the chemical composition of the meat or pig performance, but it did influence the lipid profile. Specifically, OL supplementation led to a significant reduction in saturated fatty acids (SFAs) and an increase in oleic acid, thus enhancing the proportion of monounsaturated fatty acids (MUFAs). Moreover, the n-6/n-3 PUFA ratio in the meat was significantly reduced, suggesting potential improvements in the nutritional and functional quality of pig meat, enhancing the nutritional and functional quality of the meat by improving its fatty acid profile.