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Identification of phenolic compounds from Zingiber offinale and their derivatives as histone deacetylase inhibitors and antioxidants

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Abstract

The aim of this study was to explore histone deacetylase inhibitory and antioxidant activities of natural products from ginger and their semi-synthetic derivatives. Two major phenolic compounds, [6]-gingerol and [6]-shogaol along with three minor phenolic compounds including [6]-gingerdione, 1-dehydro-[6]-gingerdione and [6]-gingerdiol were isolated and tested against histone deacetylase in HeLa nuclear extract. All compounds exhibited histone deacetylase inhibitory activities in micromolar concentrations. 1-dehydro-[6]-gingerdione showed the best inhibition with IC50 value of 42 μM. Thirteen semi-synthetic derivatives of two major natural products were synthesized and tested. The demethylated [6]-shogaol derivative was the best inhibitor among the synthesized compounds with IC50 value of 45 μM. Molecular docking experiments of selected compounds with representatives of class I and class II histone deacetylase isoforms revealed potential isoform-selective histone deacetylase inhibitors. The DPPH assay indicated that most derivatives possessed antioxidant activities superior to their lead compounds. Therefore, the studied compounds could serve as promising leads for safe and selective anticancer agents with histone deacetylase inhibitory and radical scavenging abilities.

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Acknowledgements

Khon Kaen University is gratefully acknowledged for the financial supports of this work (Grant Numbers 580403 and 592304). We also would like to thank Mr. Kittisak Poopasith for the excellent NMR data. A graduate fellowship given to Pakit Kumboonma is supported by Rajamangala University of Technology Isan (RMUTI).

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Authors and Affiliations

  1. Natural Products Research Unit, Department of Chemistry, Faculty of Science, Khon Kaen University, Khon Kaen, 40002, Thailand

    Pakit Kumboonma, 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

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  1. Pakit Kumboonma
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  2. Thanaset Senawong
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  3. Somprasong Saenglee
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  4. Chavi Yenjai
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Correspondence to Chanokbhorn Phaosiri.

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Kumboonma, P., Senawong, T., Saenglee, S. et al. Identification of phenolic compounds from Zingiber offinale and their derivatives as histone deacetylase inhibitors and antioxidants. Med Chem Res 26, 650–661 (2017). https://doi.org/10.1007/s00044-017-1785-1

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