摘要：The novel hydroxamates containing purine scaffold were designed, synthesized and screened for their biological activities as histone deacetylase (HDAC) inhibitors. Some of them exhibited excellent acti-HDACs activities and antiproliferative activities, the most promising compound was 7m′ . Western blot analysis indicated the compounds 7f′ , 7l′ , 7m′ , 7o′ could increase histone H3 acetylation levels in HCT116 and K562 cell lines, and 7m′ increased the level of acetyl histone H3 in a dose-dependent manner, which is similar to the behavior of suberoylanilide hydroxamic acid ( SAHA ). Molecular docking study revealed that the conformation of 7m′ in the active site of HDAC2 was similar to positive drug SAHA , which were oriented with the hydroxamic acid towards the catalytic center and formed metal binding with zinc ion.
关键词：hydroxamic acid;purine;histone deacetylase;antiproliferative;Western blot analysis
