-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 and , which exhibited potent inhibitory activity against HDACs (HDAC1: IC = 22 and 9 nM; HDAC6: 8 and 14 nM, respectively). In cellular levels, and significantly inhibited cell proliferation of five tumour cell lines (IC: 0.79 - 4.42 µM). Preliminary mechanistic studies indicated that and efficiently induced cell apoptosis. Unexpectedly, compound could also stimulate cell cycle arrest in G1 phase. Further study in WSU-DLCL-2 xenografted mouse model validated the antitumor activities of , without significant toxicity. The results suggest the therapeutic potential of these HDACs inhibitors in lymphoma and provide valuable insight and understanding for further structural optimisation around -elemene scaffold.
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| http://dx.doi.org/10.1080/14756366.2023.2195991 | DOI Listing |
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