Synthesis and HDAC1 Inhibitory Activity of a Novel Series of Coumarin-Based Amide Derivatives for Treatment of Cancer

Abstract

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 GI₅₀ values of 0.294 and 0.264 μM against MOLT-4 and LOX-IMVI, respectively; whereas 5u had GI₅₀ values of 0.189 and 0.263 μM, respectively. Both derivatives showed better activity than entinostat and suberoylanilide hydroxamic acid. Compound 5k exhibited an IC₅₀ value of 1.00 μM on ACHN cells. Conclusion: Coumarin derivatives exhibited promising HDAC1 inhibitory potential and warrant future development as anticancer agents.

Keywords:

• anticancer
• cinnamide
• coumarin
• docking
• HDAC1
• TNF-α

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at:www.tandfonline.com/doi/full/10.2217/epi-2016-0184

Acknowledgements

The authors are thankful to the US National Cancer Institute for in vitro anticancer screening of the compounds. The authors thank the Department of Pharmaceutical Chemistry, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi, for providing the necessary facilities.

Financial & competing interests disclosure

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors are grateful to the Department of Science and Technology for providing financial assistance under DST-WOS-A scheme with file no. SR/WOS-A/CS-101/2017, Government of India. The authors also acknowledge the Department of Science and Technology for providing financial assistance to their department under SR/FST/LS-I/2018/151. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.