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Evaluation and molecular docking study of two flavonoids from Oroxylum indicum (L.) Kurz and their semi-synthetic derivatives as histone deacetylase inhibitors

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Abstract

Chrysin (5,7-dihydroxyflavone, 6) and galangin 3-methyl ether (5,7-dihydroxy-3-methoxy flavone, 7) were obtained from the leaves of Oroxylum indicum (L.) Kurz in 4% and 6% yields, respectively. Both compounds could act as pan-histone deacetylase (HDAC) inhibitors. Structural modification of these lead compounds provided thirty-eight derivatives which were further tested as HDAC inhibitors. Compounds 6b, 6c, and 6q were the most potent derivatives with the IC50 values of 97.29 ± 0.63 μM, 91.71 ± 0.27 μM, and 96.87 ± 0.45 µM, respectively. Molecular docking study indicated the selectivity of these three compounds toward HDAC8 and the test against HDAC8 showed IC50 values in the same micromolar range. All three compounds were further evaluated for the anti-proliferative activity against HeLa and A549 cell lines. Compound 6q exhibited the best activity against HeLa cell line with the IC50 value of 13.91 ± 0.34 μM. Moreover, 6q was able to increase the acetylation level of histone H3. These promising HDAC inhibitors deserve investigation as chemotherapeutic agents for treating cancer.

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Acknowledgements

This research was supported by the Fundamental Fund of Khon Kaen University and the National Science, Research, and Innovation Fund (FF2566). We also would like to thank Mr. Kittisak Poopasith for the excellent NMR data. We were thankful to the Mr. Sookkawath Walunchapruk for the anti-proliferative activity. A graduate fellowship given to La-or Somsakeesit was supported by Rajamangala University of Technology Isan (RMUTI). Center of Excellence for Innovation in Chemistry (PERCH-CIC) and Ministry of Higher Education, Science, Research and Innovation are also gratefully acknowledged.

Funding

This study was supported by Fundamental Fund of Khon Kaen University and the National Science, Research, and Innovation Fund (FF2566).

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Authors and Affiliations

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

    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, Gulsiri Senawong, Arunta Samankul & Narissara Namwan

  3. Department of Applied Chemistry, Faculty of Science and Liberal Arts, Rajamangala University of Technology Isan, Nakhon Ratchasima, 30000, Thailand

    Pakit Kumboonma

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  1. La-or Somsakeesit
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  2. Thanaset Senawong
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  3. Gulsiri Senawong
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  4. Pakit Kumboonma
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  6. Narissara Namwan
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Contributions

La-or Somsakeesit: isolation, synthesis, structure elucidation, and drafting manuscript. Thanaset Senawong: HDAC inhibitory test and discussion. Gulsiri Senawong and Narissara Namwan: anti-proliferative activity and discussion. Pakit Kumboonma: molecular docking study. Arunta Samankul: western blot analysis. Chavi Yenjai: structure discussion and proofread. Chanokbhorn Phaosiri: concept, experimental design, finding grant, discussion, correction, and proofread.

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Correspondence to Chanokbhorn Phaosiri.

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Somsakeesit, Lo., Senawong, T., Senawong, G. et al. Evaluation and molecular docking study of two flavonoids from Oroxylum indicum (L.) Kurz and their semi-synthetic derivatives as histone deacetylase inhibitors. J Nat Med 78, 236–245 (2024). https://doi.org/10.1007/s11418-023-01758-y

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