Minor structural modifications to Pracinostat produce big changes in its biological responses

Abstract

A series of compounds similar to Pracinostat that contained benzimidazole ring and N-hydroxyacrylamide attached at 5-or 6-position were designed, synthesized, and evaluated as HDAC inhibitors. It was interesting to find that the corresponding derivative 1 with N-hydroxyacrylamide attached at 5-position was a potent HDAC inhibitor while the others at 6-position were not. This is the first time to demonstrate the position difference plays important role in the HDAC inhibitory activities of the cinnamic hydroxamates. K E Y W O R D S HDAC inhibitors, histone deacetylases, hydroxamic acids, Pracinostat, synthesisThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.