Design, synthesis and biological evaluation of novel histone deacetylase (HDAC) inhibitors derived from β-elemene scaffold.

ABSTRACT: β-Elemene is the major active ingredient of TCM anticancer drug elemene extracts. To further improve its antitumor activity and poor solubility, a polar HDACi pharmacophore was incorporated its scaffold. Systematic SAR studies led to the discovery of compounds 27f and 39f, which exhibited potent inhibitory activity against HDACs (HDAC1: IC₅₀ = 22 and 9 nM; HDAC6: 8 and 14 nM, respectively). In cellular levels, 27f and 39f significantly inhibited cell proliferation of five tumour cell lines (IC₅₀: 0.79 - 4.42 µM). Preliminary mechanistic studies indicated that 27f and 39f efficiently induced cell apoptosis. Unexpectedly, compound 39f could also stimulate cell cycle arrest in G1 phase. Further in vivo study

SUBMITTER: Gao Y 

PROVIDER: S-EPMC10075517 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature