• Sirtuins
• Sirt1 activators
• Sirt1

Sirtuins (SIRTs) are a family of proteins belonging to the third class of Histone deacetylase and ribosyl- transferase enzymes, with a NAD+-dependent activity and prokaryotic Sirtuins includes seven isoforms (SIRT1-SIRT7).
Since their discovery, Sirtuins have been studied with a very broad interest due to the role of protein Sir2 ('silent mating-type information regulation 2') in a possible lifespan extension in Saccharomyces Cerevisiae yeast. In particular, Sir2 was found to be involved in modulation of a number of cellular processes, such as cell cycle, apoptosis, inflammation and cellular ageing.
The most widely studied to date and the closest to yeast Sir2 isoform is SIRT1, mainly located in the nucleus. This enzyme has many targets in a large number of organs, thus playing key-roles in several physiological and pathological conditions as cardiovascular disorders, neurodegenerative diseases (Parkinson’s, Alzheimer), metabolic diseases and cancer cells growth.
Due to the different nature of SIRT1 targets, conflicting data show a link between SIRT1 activation and a cancer risk improvement, a higher possibility of Fragile X Syndrome development and HIV proliferation, and these controversial evidences have so far led to a large amount of studies concerning modulation of the enzyme as potential therapeutic intervention. A number of activators and inhibitors have been already discovered and the research is still ongoing, in order to improve some pharmacokinetics and pharmacodynamics features, such as bioavailability, stability, side effects and activity of well-known modulators. To this purpose, structural modifications of polyphenolic derivatives (that have been previously found to possess SIRT1 activating properties in the laboratories where I did my work), in order to synthesize novel SIRT1 activators, represent the target of my thesis project.