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<p>In this study, we successfully designed and synthesized a new series of coumarin-based hydroxamate derivatives as potent histone deacetylase (HDAC) inhibitors. Among them, several compounds showed strong inhibitory effects on whole-cell HDAC and exhibited moderate to significant antiproliferative activity against three human cancer cell lines, including MCF-7, A549 and SK-Lu-1. Notably, compounds <b>4c</b> and <b>4</b> <b>d</b> emerged as the most promising candidates. They inhibited HDAC with an IC<sub>50</sub> of 0.16 and 0.33 µM respectively, outperforming suberoylanilide hydroxamic acid (SAHA) (IC<sub>50</sub> = 0.63 µM) and demonstrated potent cytotoxicity against MCF-7 cancer cell line – from 1.2 to 6.8 times stronger than SAHA. Docking simulations further clarified their interactions with HDAC isoforms and explained its binding profile. Taken together, these findings highlight compound <b>4c</b> and <b>4</b> <b>d</b> as highly promising HDAC inhibitors with significant therapeutic potential in cancer treatment.</p><p></p>

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Design, synthesis and biological evaluation of novel hydroxamic acids bearing coumarin moieties as histone deacetylase inhibitors and cytotoxic agents

  • 期刊论文

  • 发表日期：

    2025年11月27日

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  • Tran Duy Thanh,
  • Luu Van Chinh,
  • Do Thi Thao,
  • Thach Lien Nguyen,
  • Hai Pham–The,
  • Tran Khac Vu

摘要

In this study, we successfully designed and synthesized a new series of coumarin-based hydroxamate derivatives as potent histone deacetylase (HDAC) inhibitors. Among them, several compounds showed strong inhibitory effects on whole-cell HDAC and exhibited moderate to significant antiproliferative activity against three human cancer cell lines, including MCF-7, A549 and SK-Lu-1. Notably, compounds 4c and 4 d emerged as the most promising candidates. They inhibited HDAC with an IC50 of 0.16 and 0.33 µM respectively, outperforming suberoylanilide hydroxamic acid (SAHA) (IC50 = 0.63 µM) and demonstrated potent cytotoxicity against MCF-7 cancer cell line – from 1.2 to 6.8 times stronger than SAHA. Docking simulations further clarified their interactions with HDAC isoforms and explained its binding profile. Taken together, these findings highlight compound 4c and 4 d as highly promising HDAC inhibitors with significant therapeutic potential in cancer treatment.