Molecular modifications on carboxylic acid derivatives as potent histone deacetylase inhibitors: Activity and docking studies

Thirty three carboxylic acid derivatives were designed to get insight into the structural requirements for histone deacetylase inhibition activity. Of these compounds, chlorogenic acid ( 1) and curcumin ( 2) which are derivatives of caffeic acid ( 3) were found to be highly potent compared to the well-known HDAC inhibitor sodium butyrate. In the light of known HDAC inhibitors, 33 carboxylic acid derivatives were tested to understand the structural requirements for HDAC inhibition activity. Several modifications were applied to develop the structure–activity relationships of carboxylic acid HDAC inhibitors. HDAC inhibition activities were investigated in vitro by using HeLa nuclear extract in a fluorimetric assay. Molecular docking was also carried out for the human HDAC8 enzyme in order to predict inhibition activity and the 3D poses of inhibitor–enzyme complexes. Of these compounds, caffeic acid derivatives such as chlorogenic acid and curcumin were found to be highly potent compared to sodium butyrate, which is a well-known HDAC inhibitor.