Histone deacetylases (HDACs) profoundly affect cellular function by catalyzing removal of acetyl groups from N-acetylated lysine residues of various protein substrates including histones, transcription factors, α-tubulin, and nuclear importers. Inhibition of HDAC activity has emerged as a promising approach for reversing the aberrant epigenetic states associated with cancer and other chronic diseases. To know the structure-activity relationship cyclic peptide HDACi with HDACs, several novel HDACis with similar cyclic tetrapeptide framework as chlamydocin were designed and synthesized. The binding functional group was protected as disulfide. The macrocyclic frameworks were modified by introducing methyl at different sites of benzene ring of phenylalanine. HDACi was tested for cytotoxic activity against three cancer cell lines, including MCF-7, Hela and 7721 cells. All the compounds demonstrated exciting antitumor abilities, and were most active against Hela with IC₅₀ at 0.1 μmol/L. The cellular shapes changed obviously, when the cells treated by HDACi.

Key words: histone deacetylase (HDACs), histone deacetylase inhibitor (HDACi), cyclic peptide, antitumor activity