Alessandra Nurisso
University of Geneva
Switzerland
Title: Identification of sirtuin inhibitorsas promising anticancer agents: from screening to activity assays
Biography
Biography: Alessandra Nurisso
Abstract
Sirtuins (SIRTs) are a family of enzymes able to catalyze the deacetylation of the N-acetyl lysines of both histone and non-histone substrates. Inhibition of their catalytic activity was recently reported in the literature as being beneficial in aging-related diseases such as cancer and neurodegeneration. By combining a structure-based virtual screening approach of highly diverse molecular libraries with fluorescence-based deacetylation assays, we identified new scaffolds for the inhibition of SIRT catalytic activity. For these compounds, all active in the low µM range, both mechanisms of inhibition and binding modes were elucidated. Moreover, physiochemical properties for passive adsorption and cytotoxicity data were investigated in vitro. We then demonstrated the capacity of these SIRT inhibitors to strongly repress angiogenesis in cells, in a Fox O-dependent fashion. Our study provided promising compounds able to target SIRTs that could be useful for both research and therapeutic purposes.