2-(Phenylsulfonyl)quinoline N-hydroxyacrylamides as potent anticancer agents inhibiting histone deacetylase.

Abstract This study reports the design and synthesis of 2-(phenylsulfonyl)quinoline N -hydroxyacrylamides ( 8a – k ). Structure-activity relationship studies focusing on regio-effect of N -hydroxyacrylamide moiety and influence of the sulfonyl linker revealed that N -hydroxy-3-[3-(quinoline-2-sulfonyl)-phenyl]-acrylamide ( 8f ) showed remarkable enzymatic and cellular activity. The GI 50 values of 8f for HL-60, HCT116, PC-3, and A549 cells were found to be 0.29, 0.08, 0.15, and 0.27 μM, respectively. The compounds are therefore more potent than FDA approved PXD-101 and SAHA. They also have an effect on the acetylation degree of histone H3 and α-tubulin. In in vivo studies, 8f showed marked inhibition of the growth of HCT116 xenografts.