Evaluation of histone deacetylase inhibitory and antiproliferative activity of piperine and its derivatives
Piperine (1) was obtained from the seeds of Piper nigrum L. It could act as a pan-histone deacetylase (HDAC) inhibitor. This lead compound was structurally modified to six derivatives that exhibited improved HDAC inhibitory activity. Based on the preliminary results, amide derivatives (1e and 1f)...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Prince of Songkla University
2022-12-01
|
| Series: | Songklanakarin Journal of Science and Technology (SJST) |
| Subjects: | |
| Online Access: | https://sjst.psu.ac.th/journal/44-6/12.pdf |
| _version_ | 1797838479296561152 |
|---|---|
| author | La-or Somsakeesit Anupong Joompang Santi Phosr Pattaravadee Srikoon Pakit Kumboonma Thanaset Senawong Chanokbhorn Phaosiri |
| author_facet | La-or Somsakeesit Anupong Joompang Santi Phosr Pattaravadee Srikoon Pakit Kumboonma Thanaset Senawong Chanokbhorn Phaosiri |
| author_sort | La-or Somsakeesit |
| collection | DOAJ |
| description | Piperine (1) was obtained from the seeds of Piper nigrum L. It could act as a pan-histone deacetylase (HDAC)
inhibitor. This lead compound was structurally modified to six derivatives that exhibited improved HDAC inhibitory activity.
Based on the preliminary results, amide derivatives (1e and 1f) with the highest HDAC inhibitory activity were further studied.
The results indicated that the derivatives 1e and 1f showed HDAC inhibitory activity with IC50 of 85.61 ± 3.32 µM and 111.27 ±
2.13 µM, respectively. A molecular docking study suggested that piperine (1) had a high selectivity for HDAC1, while 1e and 1f
showed high selectivity for HDAC2. These derivatives were predicted to interact with HDAC active site using hydrogen bond,
hydrophobic interaction, as well as chelation with Zn2+
. The antiproliferative activity obtained from MTT assay against the HeLa
cell line indicated that 1f potentially inhibits HeLa cells with an IC50 of 10.38 ± 2.13 g/mL. These results suggest potential
HDAC inhibitors for further development to anti-cancer agents. |
| first_indexed | 2024-04-09T15:41:31Z |
| format | Article |
| id | doaj.art-fb0291b4a4874c05b059ffa285edfd17 |
| institution | Directory Open Access Journal |
| issn | 0125-3395 |
| language | English |
| last_indexed | 2024-04-09T15:41:31Z |
| publishDate | 2022-12-01 |
| publisher | Prince of Songkla University |
| record_format | Article |
| series | Songklanakarin Journal of Science and Technology (SJST) |
| spelling | doaj.art-fb0291b4a4874c05b059ffa285edfd172023-04-27T09:45:52ZengPrince of Songkla UniversitySongklanakarin Journal of Science and Technology (SJST)0125-33952022-12-014461481148810.14456/sjst-psu.2022.192Evaluation of histone deacetylase inhibitory and antiproliferative activity of piperine and its derivativesLa-or Somsakeesit0Anupong Joompang1Santi Phosr2Pattaravadee Srikoon3Pakit Kumboonma4Thanaset Senawong5Chanokbhorn Phaosiri6Department of Chemistry, Faculty of Engineering, Rajamangala University of Technology Isan Khon Kaen Campus, Mueang, Khon Kaen, 40000 ThailandFaculty of Pharmaceutical Sciences, Burapha University, Mueang, Chonburi, 20131 ThailandDepartment of Chemical Engineering, Faculty of Engineering, Burapha University, Mueang, Chonburi, 20131 ThailandFaculty of Pharmaceutical Sciences, Burapha University, Mueang, Chonburi, 20131 ThailandDepartment of Applied Chemistry, Faculty of Science and Liberal Arts, Rajamangala University of Technology Isan, Mueang, Nakhon Ratchasima, 30000 ThailandNatural Products Research Unit, Department of Biochemistry, Faculty of Science, Khon Kaen University, Mueang, Khon Kaen, 40002 ThailandNatural Products Research Unit, Department of Chemistry, Faculty of Science, Khon Kaen University, Mueang, Khon Kaen, 40002 ThailandPiperine (1) was obtained from the seeds of Piper nigrum L. It could act as a pan-histone deacetylase (HDAC) inhibitor. This lead compound was structurally modified to six derivatives that exhibited improved HDAC inhibitory activity. Based on the preliminary results, amide derivatives (1e and 1f) with the highest HDAC inhibitory activity were further studied. The results indicated that the derivatives 1e and 1f showed HDAC inhibitory activity with IC50 of 85.61 ± 3.32 µM and 111.27 ± 2.13 µM, respectively. A molecular docking study suggested that piperine (1) had a high selectivity for HDAC1, while 1e and 1f showed high selectivity for HDAC2. These derivatives were predicted to interact with HDAC active site using hydrogen bond, hydrophobic interaction, as well as chelation with Zn2+ . The antiproliferative activity obtained from MTT assay against the HeLa cell line indicated that 1f potentially inhibits HeLa cells with an IC50 of 10.38 ± 2.13 g/mL. These results suggest potential HDAC inhibitors for further development to anti-cancer agents.https://sjst.psu.ac.th/journal/44-6/12.pdfpiper nigrum l.piperinepiperine derivativehdachela cell |
| spellingShingle | La-or Somsakeesit Anupong Joompang Santi Phosr Pattaravadee Srikoon Pakit Kumboonma Thanaset Senawong Chanokbhorn Phaosiri Evaluation of histone deacetylase inhibitory and antiproliferative activity of piperine and its derivatives Songklanakarin Journal of Science and Technology (SJST) piper nigrum l. piperine piperine derivative hdac hela cell |
| title | Evaluation of histone deacetylase inhibitory and antiproliferative activity of piperine and its derivatives |
| title_full | Evaluation of histone deacetylase inhibitory and antiproliferative activity of piperine and its derivatives |
| title_fullStr | Evaluation of histone deacetylase inhibitory and antiproliferative activity of piperine and its derivatives |
| title_full_unstemmed | Evaluation of histone deacetylase inhibitory and antiproliferative activity of piperine and its derivatives |
| title_short | Evaluation of histone deacetylase inhibitory and antiproliferative activity of piperine and its derivatives |
| title_sort | evaluation of histone deacetylase inhibitory and antiproliferative activity of piperine and its derivatives |
| topic | piper nigrum l. piperine piperine derivative hdac hela cell |
| url | https://sjst.psu.ac.th/journal/44-6/12.pdf |
| work_keys_str_mv | AT laorsomsakeesit evaluationofhistonedeacetylaseinhibitoryandantiproliferativeactivityofpiperineanditsderivatives AT anupongjoompang evaluationofhistonedeacetylaseinhibitoryandantiproliferativeactivityofpiperineanditsderivatives AT santiphosr evaluationofhistonedeacetylaseinhibitoryandantiproliferativeactivityofpiperineanditsderivatives AT pattaravadeesrikoon evaluationofhistonedeacetylaseinhibitoryandantiproliferativeactivityofpiperineanditsderivatives AT pakitkumboonma evaluationofhistonedeacetylaseinhibitoryandantiproliferativeactivityofpiperineanditsderivatives AT thanasetsenawong evaluationofhistonedeacetylaseinhibitoryandantiproliferativeactivityofpiperineanditsderivatives AT chanokbhornphaosiri evaluationofhistonedeacetylaseinhibitoryandantiproliferativeactivityofpiperineanditsderivatives |