Design, synthesis and preliminary biological evaluation of N-hydroxy-4-(3-phenylpropanamido)benzamide (HPPB) derivatives as novel histone deacetylase inhibitors.

A novel series of N-hydroxy-4-(3-phenylpropanamido)benzamide (HPPB) derivatives comprising N-hydroxybenzamide group as zinc-chelating moiety were designed, synthesized and evaluated for their ability to inhibit histone deacetylases. These compounds possessed inhibitory activity against the enzymes with IC(50) values as low as 4.0 microM. Among them, the thiophene substituted derivative 5j (IC(50)=0.3 microM) and benzo[d][1,3]dioxole derivative 5t (IC(50)=0.4 microM) exhibited good antiproliferative activity against the growth of human colon carcinoma cell line HCT116 and non-small cell lung cancer cell (NSCLC) line A549. In addition, they were found to potently induce cell-cycle arrest at G2 phase.