Histone Deacetylase Inhibitory Activity and Antiproliferative Potential of New [6]-Shogaol Derivatives
Twenty newly synthesized derivatives of [6]-shogaol (<b>4</b>) were tested for inhibitory activity against histone deacetylases. All derivatives showed moderate to good histone deacetylase inhibition at 100 µM with a slightly lower potency than the lead compound. Most potent inhibitors a...
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MDPI AG
2022-05-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/10/3332 |
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| author | Chanokbhorn Phaosiri Chavi Yenjai Thanaset Senawong Gulsiri Senawong Somprasong Saenglee La-or Somsakeesit Pakit Kumboonma |
| author_facet | Chanokbhorn Phaosiri Chavi Yenjai Thanaset Senawong Gulsiri Senawong Somprasong Saenglee La-or Somsakeesit Pakit Kumboonma |
| author_sort | Chanokbhorn Phaosiri |
| collection | DOAJ |
| description | Twenty newly synthesized derivatives of [6]-shogaol (<b>4</b>) were tested for inhibitory activity against histone deacetylases. All derivatives showed moderate to good histone deacetylase inhibition at 100 µM with a slightly lower potency than the lead compound. Most potent inhibitors among the derivatives were the pyrazole products, <b>5j</b> and <b>5k,</b> and the Michael adduct with pyridine <b>4c</b> and benzothiazole <b>4d,</b> with IC<sub>50</sub> values of 51, 65, 61 and 60 µM, respectively. They were further evaluated for isoform selectivity via a molecular docking study. Compound <b>4d</b> showed the best selectivity towards HDAC3, whereas compound <b>5k</b> showed the best selectivity towards HDAC2. The potential derivatives were tested on five cancer cell lines, including human cervical cancer (HeLa), human colon cancer (HCT116), human breast adenocarcinoma cancer (MCF-7), and cholangiocarcinoma (KKU100 and KKU-M213B) cells with MTT-based assay. The most active histone deacetylase inhibitor <b>5j</b> exhibited the best antiproliferative activity against HeLa, HCT116, and MCF-7, with IC<sub>50</sub> values of 8.09, 9.65 and 11.57 µM, respectively, and a selective binding to HDAC1 based on molecular docking experiments. The results suggest that these compounds can be putative candidates for the development of anticancer drugs via inhibiting HDACs. |
| first_indexed | 2024-03-10T03:18:15Z |
| format | Article |
| id | doaj.art-350cf8cd211542be831d2503c15d52bf |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T03:18:15Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-350cf8cd211542be831d2503c15d52bf2023-11-23T12:24:46ZengMDPI AGMolecules1420-30492022-05-012710333210.3390/molecules27103332Histone Deacetylase Inhibitory Activity and Antiproliferative Potential of New [6]-Shogaol DerivativesChanokbhorn Phaosiri0Chavi Yenjai1Thanaset Senawong2Gulsiri Senawong3Somprasong Saenglee4La-or Somsakeesit5Pakit Kumboonma6Natural 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, ThailandNatural 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, ThailandNatural Products Research Unit, Department of Biochemistry, Faculty of Science, Khon Kaen University, Khon Kaen 40002, ThailandNatural Products Research Unit, Department of Biochemistry, Faculty of Science, Khon Kaen University, Khon Kaen 40002, ThailandBan Dong Sub-District Administration Organization, Ubolratana District, Khon Kaen 40250, ThailandDepartment of Chemistry, Faculty of Engineering, Rajamangala University of Technology Isan, Khon Kaen 40000, ThailandDepartment of Applied Chemistry, Faculty of Science and Liberal Arts, Rajamangala University of Technology Isan, Nakhon Ratchasima 30000, ThailandTwenty newly synthesized derivatives of [6]-shogaol (<b>4</b>) were tested for inhibitory activity against histone deacetylases. All derivatives showed moderate to good histone deacetylase inhibition at 100 µM with a slightly lower potency than the lead compound. Most potent inhibitors among the derivatives were the pyrazole products, <b>5j</b> and <b>5k,</b> and the Michael adduct with pyridine <b>4c</b> and benzothiazole <b>4d,</b> with IC<sub>50</sub> values of 51, 65, 61 and 60 µM, respectively. They were further evaluated for isoform selectivity via a molecular docking study. Compound <b>4d</b> showed the best selectivity towards HDAC3, whereas compound <b>5k</b> showed the best selectivity towards HDAC2. The potential derivatives were tested on five cancer cell lines, including human cervical cancer (HeLa), human colon cancer (HCT116), human breast adenocarcinoma cancer (MCF-7), and cholangiocarcinoma (KKU100 and KKU-M213B) cells with MTT-based assay. The most active histone deacetylase inhibitor <b>5j</b> exhibited the best antiproliferative activity against HeLa, HCT116, and MCF-7, with IC<sub>50</sub> values of 8.09, 9.65 and 11.57 µM, respectively, and a selective binding to HDAC1 based on molecular docking experiments. The results suggest that these compounds can be putative candidates for the development of anticancer drugs via inhibiting HDACs.https://www.mdpi.com/1420-3049/27/10/3332ginger<i>Zingiber officinale</i>[6]-shogaol derivativesanticancermolecular docking |
| spellingShingle | Chanokbhorn Phaosiri Chavi Yenjai Thanaset Senawong Gulsiri Senawong Somprasong Saenglee La-or Somsakeesit Pakit Kumboonma Histone Deacetylase Inhibitory Activity and Antiproliferative Potential of New [6]-Shogaol Derivatives Molecules ginger <i>Zingiber officinale</i> [6]-shogaol derivatives anticancer molecular docking |
| title | Histone Deacetylase Inhibitory Activity and Antiproliferative Potential of New [6]-Shogaol Derivatives |
| title_full | Histone Deacetylase Inhibitory Activity and Antiproliferative Potential of New [6]-Shogaol Derivatives |
| title_fullStr | Histone Deacetylase Inhibitory Activity and Antiproliferative Potential of New [6]-Shogaol Derivatives |
| title_full_unstemmed | Histone Deacetylase Inhibitory Activity and Antiproliferative Potential of New [6]-Shogaol Derivatives |
| title_short | Histone Deacetylase Inhibitory Activity and Antiproliferative Potential of New [6]-Shogaol Derivatives |
| title_sort | histone deacetylase inhibitory activity and antiproliferative potential of new 6 shogaol derivatives |
| topic | ginger <i>Zingiber officinale</i> [6]-shogaol derivatives anticancer molecular docking |
| url | https://www.mdpi.com/1420-3049/27/10/3332 |
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