Design, synthesis, and preliminary bioactivity studies of substituted purine hydroxamic acid derivatives as novel histone deacetylase (HDAC) inhibitors

Abstract

Histone deacetylase (HDAC) is a clinically validated target for anti-tumor therapy. In order to increase HDAC inhibition and efficiency, we developed a series of novel substituted purine hydroxamic acids as potent HDAC inhibitors. The biological evaluation suggests that compound 5r (IC₅₀ = 0.075 μmol L⁻¹) exhibits better HDAC1 and 2 inhibitory activity compared to the approved drug SAHA (IC₅₀ = 0.14 μmol L⁻¹). Further biological evaluation indicated that compounds 5r, 5w, and 5x have potent anti-proliferative activities against eight tumor cells, including MDA-MB231, KG1, PC3, U937 and so on.