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New histone deacetylase inhibitors and anticancer agents from Curcuma longa

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Abstract

The aims of this study were to explore histone deacetylase inhibitory and antioxidant activities of curcuminoids as well as derivatives of curcumin. Curcumin (6), demethoxycurcumin (7), dihydrocurcumin (8), bisdemethoxycurcumin (9), and hydroxycurcumin (10) were isolated and tested against histone deacetylases in HeLa nuclear extract. Hydroxycurcumin (10) showed the best inhibition among the isolated compounds. Some curcumin derivatives were also prepared and tested. The potential derivatives were tested on five cancer cell lines. All compounds exhibited slightly weaker antiproliferative activities against cancer cells and less toxic to non-cancer cells than curcumin (6). The least toxic derivative (17) exhibited the best antiproliferative activity against human cervical cancer cell lines (HeLa) with the IC50 value of 4.69 ± 0.14 μM. The most active histone deacetylase inhibitor (19) showed the highest potency against human colon cancer cell lines (HCT116) and the selective binding to HDAC4 based on molecular docking experiments. Most derivatives possessed antioxidant activities superior to curcumin. The results suggested potential candidates for anticancer agents.

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Acknowledgements

Khon Kaen University is gratefully acknowledged for the financial support of this work (Grant Number 6200014002). We also would like to thank Mr. Kittisak Poopasith for the excellent NMR data. We are thankful to the Postdoctoral Training Program, Graduate School, Khon Kaen University for providing a fellowship to Dr. Somprasong Saenglee. A graduate fellowship given to Pakit Kumboonma and La-or Somsakeesit is supported by Rajamangala University of Technology Isan (RMUTI).

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Authors and Affiliations

  1. Natural Products Research Unit, Center of Excellence for Innovation in Chemistry, Ministry of Higher Education, Science, Research and Innovation (Implementation Unit-IU, Khon Kaen University), Department of Chemistry, Faculty of Science, Khon Kaen University, Khon Kaen, 40002, Thailand

    Pakit Kumboonma, La-or Somsakeesit, Chavi Yenjai & Chanokbhorn Phaosiri

  2. Natural Products Research Unit, Department of Biochemistry, Faculty of Science, Khon Kaen University, Khon Kaen, 40002, Thailand

    Thanaset Senawong, Somprasong Saenglee & Gulsiri Senawong

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  1. Pakit Kumboonma
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  2. Thanaset Senawong
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  4. Gulsiri Senawong
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Correspondence to Chanokbhorn Phaosiri.

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Kumboonma, P., Senawong, T., Saenglee, S. et al. New histone deacetylase inhibitors and anticancer agents from Curcuma longa. Med Chem Res 28, 1773–1782 (2019). https://doi.org/10.1007/s00044-019-02414-5

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