Zinc binding group(ZBG)is the crucial moiety in the chemical structure of any HDAC inhibitor.In the present study,a series of sulphur-containing ZBG were designed and synthesized in the novel HDAC inhibitors to replac...Zinc binding group(ZBG)is the crucial moiety in the chemical structure of any HDAC inhibitor.In the present study,a series of sulphur-containing ZBG were designed and synthesized in the novel HDAC inhibitors to replace the classical ZBGs of SAHA and BML-210,hydroxamic acids and benzamides,respectively.The HDAC inhibitory activity and the structure-activity relationships of these molecules were analyzed.A sulphur-rich group,diethylcarbamo(dithioperoxo)thioate,was finally identified as a novel potent ZBG.Among all the synthesized compounds,4 d was much more potent compared with BML-210,and it showed similar inhibitory effect of SAHA against HDAC isoforms 1 and 2.Therefore,it was chosen as a lead compound.展开更多
基金National Natural Science Foundation of China(Grant No.81573272)
文摘Zinc binding group(ZBG)is the crucial moiety in the chemical structure of any HDAC inhibitor.In the present study,a series of sulphur-containing ZBG were designed and synthesized in the novel HDAC inhibitors to replace the classical ZBGs of SAHA and BML-210,hydroxamic acids and benzamides,respectively.The HDAC inhibitory activity and the structure-activity relationships of these molecules were analyzed.A sulphur-rich group,diethylcarbamo(dithioperoxo)thioate,was finally identified as a novel potent ZBG.Among all the synthesized compounds,4 d was much more potent compared with BML-210,and it showed similar inhibitory effect of SAHA against HDAC isoforms 1 and 2.Therefore,it was chosen as a lead compound.
