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 ₅₀ values of 0.294 and 0.264 μM against MOLT-4 and LOX-IMVI, respectively; whereas 5u had GI ₅₀ values of 0.189 and 0.263 μM, respectively. Both derivatives showed better activity than entinostat and suberoylanilide hydroxamic acid. Compound 5k exhibited an IC ₅₀ value of 1.00 μM on ACHN cells. Conclusion: Coumarin derivatives exhibited promising HDAC1 inhibitory potential and warrant future development as anticancer agents.