Synthesis and HDAC1 inhibitory activity of a novel series of coumarin-based amide derivatives for treatment of cancer

Background: Histone deacetylases (HDACs) play a vital role in the epigenetic regulation of transcription and expression. HDAC1 overexpression is seen in many cancers. Methodology: The authors synthesized and evaluated 27 novel coumarin-based amide derivatives for HDAC1 inhibitory activity. The compounds were screened at the US National Cancer Institute, and 5k and 5u were selected for five-dose assays. Compound 5k showed GI(5)0 values of 0.294 and 0.264 mu M against MOLT-4 and LOX-IMVI, whereas 5u had GI50 values of 0.189 and 0.263 mu M, respectively. Both derivatives showed better activity than entinostat and suberoylanilide hydroxamic acid. Compound 5k exhibited an IC50 value of 1.00 mu M on ACHN cells. Conclusion: Coumarin derivatives exhibited promising HDAC1 inhibitory potential and warrant future development as anticancer agents.

Automated summary

In this study, the authors synthesized and evaluated 27 novel coumarin-based amide derivatives for their HDAC1 inhibitory activity. They found that two of the compounds showed better activity than existing drugs. These coumarin derivatives exhibited promising potential as anticancer agents and should be further developed.