Synthesis, Evaluation and Molecular Modeling Study of L-2-amino-7/8-Bromoalkanoic Acid Derivatives as Histone Deacetylase Inhibitors

摘要

@@ Modulation of the acetylation state of lysine residues in the N-terminal of core histones plays a pivotal role in the regulation of gene expression[1,2]. Acetylation and deacetylation of histones are controlled by two corresponding enzymes, histone acetyltransferases (HATs) and histone deacetylases (HDACs)'31. In general, HDACs activity relates to transcriptional repression, and abnormal increase in HDACs activity has been associated with the development of some human cancers[4]. Studies indicated that inhibiting HDACs in tumor cells can induce growth arrest, cell proliferation and apoptosis. Therefore HDAC inhibitors (HDACIs) have become a promising class of anticancer agents[5]. Some natural and synthetic compounds have been reported as HDACIs. Almost all HDACIs are comprised of three parts: metal binding, linker and surface recognition domains[6].