Identification of novel SIRT2-selective inhibitors using a click chemistry approach

A series of 114 SIRT inhibitor candidates was assembled using ‘click chemistry’, by reacting two alkynes bearing 2-anilinobenzamide pharmacophore with 57 azide building blocks in the presence of Cu(I) catalyst. Screening identified two SIRT2-selective inhibitors, which were more SIRT2-selective than AGK2, a known SIRT2 inhibitor. These findings will be useful for further development of SIRT2-selective inhibitors.

Graphical abstractTo find novel SIRT2-selective inhibitors, we designed and prepared a library of SIRT inhibitor candidates derived from CuAAC reaction between propargyl 2-anilinobenzamides A and a series of azides B. Screening identified SIRT2-selective inhibitors A1B11 and A2B57, which were more SIRT2-selective than AGK2 (1), a known SIRT2 inhibitor. These findings will be useful in the further development of SIRT2-selective inhibitors.Figure optionsDownload full-size imageDownload as PowerPoint slide