57. Exploiting new Se-glycoconjugates as antioxidant supplements in oxidative stress related diseases

The primary driver of cellular senescence is reactive oxygen species (ROS) formation, which leads to oxidative stress (OS) and inflammation and is involved in the pathogenesis of many health conditions, such as chronic diseases, neurodegenerative diseases, or cancer. OS is characterised by an imbalance between the damage caused by ROS and the antioxidant defences of the organism [1]. Natural sources of dietary antioxidants are essential to counteract this condition because human defence mechanisms cannot fully protect against ROS damage [2]. Diet is an important environmental factor and a potential tool for the control of these pathologies supported by clear evidence. As an additional health benefit, nutraceuticals may be used to prevent OS [3]. In this context we focused on Selenium (Se) and polyphenols. The first one is an essential nutrient able to modify physiological changes induced by OS, preventing disease, and promoting healthy ageing [1]. Polyphenols are well-known class of phytochemicals whose consumption is considered linked to reduction in chronic diseases risk factors. Their bioavailability, however, is a controversial weak point coming from to interactions with the food matrix, metabolic processes mediated by the liver, intestine, and microbiota, and other factors [4]. Glycosylation modifies the chemical, biological, and physical properties of polyphenols, enhancing their small intestine absorption [5]. Within this framework, our research is centred on the synthesis of Se-based compounds featured by a sugar-type structure linked to (poly)phenols. The novel molecules would be overcome the limited bioavailability and provide a synergistic antioxidant effect at once. The synthetic strategy proposed starts from D-ribose derivative 1 to obtain the donor 2, which is then used to produce glycoconjugates via a Mitsunobu reaction with well-known (poly)phenols [6]. Selenoglycoconjugates were evaluated for radical scavenging activity using DPPH and ABTS assays. In addition, mitochondrial redox activity and the effects on cell proliferation were evaluated using the MTT assay on neuroblastoma cells line (SH-SY5Y). Both antiradical and mitochondrial redox activity were significantly influenced by the different phenolic moiety. Highlighting the moderating effect of selenosugar, glycoconjugates had less cytotoxic effects than unconjugated phenolic compounds, especially at the highest tested doses.