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Design, synthesis and antitumor activity evaluation of novel benzamide HDAC inhibitors

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Abstract

In recent years, histone deacetylase (HDAC) has become one of the hottest and most effective targets for the treatment of cancer. In this work, we designed and synthesized a series of novel o-aminobenzamide based HDAC inhibitors and evaluated their antitumor properties in vitro. All 23 compounds obtained showed micromolar IC50 values against A549 cells proliferation, and the most effective compound was 8 u (IC50 = 0.165 μM). In vitro, 8 u showed potent antiproliferative activity against another three cancer cell lines, outperforming the approved drug Chidamide. Enzyme inhibition and western blot assays confirmed that 8 u was a selective inhibitor of HDAC1-3 isoforms. 8 u was able to induce apoptosis of A549 cells and arrest the tumor cells in G2/M phase. Moreover, 8 u significantly mitigated the migration A549 cells. All these results suggest that 8 u deserves further biological studies.

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Acknowledgements

This work was supported by the National Science Foundation for Young Scientists of China to Yepeng Luan (NSFC No.81602947).

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  1. Department of Medicinal Chemistry, School of Pharmacy, Medical College, Qingdao University, Qingdao, Shandong, China

    Ci Cai & Yepeng Luan

  2. Department of Pharmacology, School of Pharmacology, Medical College, Qingdao University, Qingdao, Shandong, China

    Ci Cai

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Cai, C., Luan, Y. Design, synthesis and antitumor activity evaluation of novel benzamide HDAC inhibitors. Med Chem Res (2024). https://doi.org/10.1007/s00044-024-03210-6

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