Synthesis of benzimidazole and benzothiazole derivatives as a sirtuins 2 inhibitor

A series of novel benzimidazole and benzothiazole derivatives were designed and synthesized as inhibitors of SIRT1-SIRT3. The target compounds were synthesized from potassium O-ethyldithiocarbonate through a three-step route. The structures of the obtained compounds were elucidated by ¹H NMR and HR-MS. Of all compounds, six showed potent SIRT2-inhibitory activities with IC₅₀ values ranging from 2.8 to 21.2 μmol·L^-1. Among them, compound 10c displayed the most potent SIRT2-inhibitory activities (IC₅₀ = 2.8 μmol·L^-1), with more than 35-fold selectivity over SIRT1 and SIRT3 (IC₅₀>100 μmol·L^-1).