Synthesis of small organic molecules as SIRT1 activators.

Sirtuins (SIRTs) are a family of NAD+-dependent protein lysine deacetylases.Mammals have seven sirtuin isoforms, SIRT1-7, which have different localizations in cell compartments, as well as different activities and targets. The most studied sirtuin isoform is SIRT1, which plays important functions in a number of pathological conditions such as inflammation, cancer, neuroprotection, metabolic disorders as diabetes, aging-related diseases, cardiovascular disorders, as well as in numerous cellular processes such as gene repression, apoptosis, and DNA repair. Due to the physiological functions and pathophysiological roles of SIRT1 in human diseases there is a great interest in the discovery of small molecules that are able to stimulate and modify SIRT1 activity. Several polyphenolic derivatives, such as pterostilbene, quercetin, myricetin, piceatannol and resveratrol (RSV), were described as among the first SIRT1 activators, which are able to induce lifespan extension and help in the treatment of metabolic disorders. In addition to the natural products, several new synthetic activators were discovered, including SRT2183, SRT1460 and SRT1720