Design, synthesis and preliminary bioactivity evaluations of substituted quinoline hydroxamic acid derivatives as novel histone deacetylase (HDAC) inhibitors.

Inhibition of HDACs activity has become a promising therapeutic strategy in clinical practice to reverse the abnormal epigenetic states of cancer and other diseases. Therefore, HDAC inhibitors become a relatively new class of anti-cancer agent. In the present study, we reported the design and synthesis of a series of novel HDAC inhibitors using various substituted quinoline rings as the cap group. In vitro studies showed that some compounds have good inhibitory activities against HDACs and potent antiproliferative activities in some tumor cell lines. Especially, compound 9w (IC50=85 nM), exhibited better inhibitory effect compared with SAHA (IC50=161 nM).