Largazole Analogues as Histone Deacetylase Inhibitors and Anticancer Agents: An Overview of Structure–Activity Relationships

Since the time of its identification, the natural compound largazole rapidly caught the attention of the medicinal chemistry community for its impressive potency as histone deacetylases (HDACs) inhibitor and its strong antiproliferative activity against a broad panel of cancer cell lines. The design of largazole analogues is an expanding field of study, due to their remarkable potential as novel anticancer therapeutics. At present, a large ensemble of largazole analogues has been reported in literature, thus allowing the identification of important structure-activity relationships (SAR) that can guide the design of novel compounds with improved HDAC inhibitory profile, anticancer activity and pharmacokinetic properties. The aim of this review is to summarize in a concise way the information obtained by the biological evaluation of the various largazole analogues reported in literature, with particular attention to the latest analogues, as well as to analyze the different SAR obtained from this data, with the purpose of providing useful guidelines for the development of novel potent and selective HDAC inhibitors to be used as anticancer agents.