Design, synthesis, and preliminary bioactivity studies of substituted purine hydroxamic acid derivatives as novel histone deacetylase (HDAC) inhibitors†
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.
- This article is part of the themed collection: Epigenetics