The balance of histone acetylation and deacetylation plays a critical role in the regulation of gene expression. Histone acetyl transferases (HATs) are associated with gene transcription, while histone deacetylases (HDACs) are associated with gene silencing. HDACs are among the most promising therapeutic targets for cancer treatment due to their regulation on cancer cell proliferation, cell-cycle regulation and apoptosis. In this study, we designed and synthesized over 40 HDAC inhibitors based on a marine natural product, santacruzamate. These compounds were tested against HDAC 1 through 11 for their inhibitory potencies and isoform selectivity. The structure-activity relationship was investigated and it was found that several structural features such as triazole and thioamide could greatly enhance the enzyme/inhibitor binding affinity.

Structure-activity relationship study on histone deacetylase (HDAC) inhibitors derived from Santacruzamate

251st National Meeting (2016)

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