Design and Synthesis of SRT1 Activators for Potential Lead Compounds of Treatment of Diabetes

Sirtuins catalyze NAD+-dependent protein deacetylation and are key regulators of transcription, apoptosis, metabolism, and aging. There are seven human sirtuins (SIRT1–7), and SIRT1 has been proven as a key mediator of the pathways downstream of calorie restriction that has been shown to delay the onset and the incidence of age-related diseases such as type II diabetes. Increasing SIRT1 activity, either by transgenic over expression of the SIRT1 gene in mice or by pharmacological activation by small molecule activator SRT1720, has shown beneficial effects in rodent models of type II diabetes. In this paper, several small molecules were designed and synthesized through a convenient synthetic procedure. Ten newly synthesized compounds were characterized on the basis of 1H NMR.