Histone deacetylases (HDACs) are important targets in cancer treatment, and the development of selective and broad-spectrum HDACs inhibitors (HDACis) is urgent. In this research, a series of aroylpiperazine hybrid derivatives were designed and synthesized. Among these, indole-piperazine hybrids 6a (IC50 = 205 nM) and 6b (IC50 = 280 nM) showed submicromolar activity against HDAC1. Moreover, 6a showed a preferable affinity toward class I HDACs, especially for HDAC1-3. In vitro, 6a exhibited better antiproliferative activities against K562 and HCT116 cell lines than chidamide.
Keywords: antitumor; histone deacetylase (HDAC) inhibitor; indole; selectivity; synthesis.