<i>O</i>-Aminoalkyl-<i>O</i>-Trimethyl-2,3-Dehydrosilybins: Synthesis and In Vitro Effects Towards Prostate Cancer Cells
As part of our ongoing silybin project, this study aims to introduce a basic nitrogen-containing group to 7-OH of 3,5,20-<i>O</i>-trimethyl-2,3-dehydrosilybin or 3-OH of 5,7,20-<i>O</i>-trimethyl-2,3-dehydrosilybin via an appropriate linker for in vitro evaluation as potentia...
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MDPI AG
2018-11-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/23/12/3142 |
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| author | Bao Vue Sheng Zhang Andre Vignau Guanglin Chen Xiaojie Zhang William Diaz Qiang Zhang Shilong Zheng Guangdi Wang Qiao-Hong Chen |
| author_facet | Bao Vue Sheng Zhang Andre Vignau Guanglin Chen Xiaojie Zhang William Diaz Qiang Zhang Shilong Zheng Guangdi Wang Qiao-Hong Chen |
| author_sort | Bao Vue |
| collection | DOAJ |
| description | As part of our ongoing silybin project, this study aims to introduce a basic nitrogen-containing group to 7-OH of 3,5,20-<i>O</i>-trimethyl-2,3-dehydrosilybin or 3-OH of 5,7,20-<i>O</i>-trimethyl-2,3-dehydrosilybin via an appropriate linker for in vitro evaluation as potential anti-prostate cancer agents. The synthetic approaches to 7-<i>O</i>-substituted-3,5,20-<i>O</i>-trimethyl-2,3-dehydrosilybins through a five-step procedure and to 3-<i>O</i>-substituted-5,7,20-<i>O</i>-trimethyl-2,3- dehydrosilybins via a four-step transformation have been developed. Thirty-two nitrogen-containing derivatives of silybin have been achieved through these synthetic methods for the evaluation of their antiproliferative activities towards both androgen-sensitive (LNCaP) and androgen-insensitive prostate cancer cell lines (PC-3 and DU145) using the WST-1 cell proliferation assay. These derivatives exhibited greater in vitro antiproliferative potency than silibinin. Among them, <b>11</b>, <b>29</b>, <b>31</b>, <b>37</b>, and <b>40</b> were identified as five optimal derivatives with IC<sub>50</sub> values in the range of 1.40⁻3.06 µM, representing a 17- to 52-fold improvement in potency compared to silibinin. All these five optimal derivatives can arrest the PC-3 cell cycle in the G<sub>0</sub>/G<sub>1</sub> phase and promote PC-3 cell apoptosis. Derivatives <b>11</b>, <b>37</b>, and <b>40</b> are more effective than <b>29</b> and <b>31</b> in activating PC-3 cell apoptosis. |
| first_indexed | 2024-12-21T01:00:21Z |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-21T01:00:21Z |
| publishDate | 2018-11-01 |
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| series | Molecules |
| spelling | doaj.art-bdb572d64a924f9b882be3abdef407362022-12-21T19:21:13ZengMDPI AGMolecules1420-30492018-11-012312314210.3390/molecules23123142molecules23123142<i>O</i>-Aminoalkyl-<i>O</i>-Trimethyl-2,3-Dehydrosilybins: Synthesis and In Vitro Effects Towards Prostate Cancer CellsBao Vue0Sheng Zhang1Andre Vignau2Guanglin Chen3Xiaojie Zhang4William Diaz5Qiang Zhang6Shilong Zheng7Guangdi Wang8Qiao-Hong Chen9Department of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenues, M/S SB70, Fresno, CA 93740, USADepartment of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenues, M/S SB70, Fresno, CA 93740, USADepartment of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenues, M/S SB70, Fresno, CA 93740, USADepartment of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenues, M/S SB70, Fresno, CA 93740, USADepartment of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenues, M/S SB70, Fresno, CA 93740, USADepartment of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenues, M/S SB70, Fresno, CA 93740, USADepartment of Chemistry and RCMI Cancer Research Center, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USADepartment of Chemistry and RCMI Cancer Research Center, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USADepartment of Chemistry and RCMI Cancer Research Center, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USADepartment of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenues, M/S SB70, Fresno, CA 93740, USAAs part of our ongoing silybin project, this study aims to introduce a basic nitrogen-containing group to 7-OH of 3,5,20-<i>O</i>-trimethyl-2,3-dehydrosilybin or 3-OH of 5,7,20-<i>O</i>-trimethyl-2,3-dehydrosilybin via an appropriate linker for in vitro evaluation as potential anti-prostate cancer agents. The synthetic approaches to 7-<i>O</i>-substituted-3,5,20-<i>O</i>-trimethyl-2,3-dehydrosilybins through a five-step procedure and to 3-<i>O</i>-substituted-5,7,20-<i>O</i>-trimethyl-2,3- dehydrosilybins via a four-step transformation have been developed. Thirty-two nitrogen-containing derivatives of silybin have been achieved through these synthetic methods for the evaluation of their antiproliferative activities towards both androgen-sensitive (LNCaP) and androgen-insensitive prostate cancer cell lines (PC-3 and DU145) using the WST-1 cell proliferation assay. These derivatives exhibited greater in vitro antiproliferative potency than silibinin. Among them, <b>11</b>, <b>29</b>, <b>31</b>, <b>37</b>, and <b>40</b> were identified as five optimal derivatives with IC<sub>50</sub> values in the range of 1.40⁻3.06 µM, representing a 17- to 52-fold improvement in potency compared to silibinin. All these five optimal derivatives can arrest the PC-3 cell cycle in the G<sub>0</sub>/G<sub>1</sub> phase and promote PC-3 cell apoptosis. Derivatives <b>11</b>, <b>37</b>, and <b>40</b> are more effective than <b>29</b> and <b>31</b> in activating PC-3 cell apoptosis.https://www.mdpi.com/1420-3049/23/12/3142silybinprostate cancer2,3-dehydrosilybincell proliferationcell apoptosis |
| spellingShingle | Bao Vue Sheng Zhang Andre Vignau Guanglin Chen Xiaojie Zhang William Diaz Qiang Zhang Shilong Zheng Guangdi Wang Qiao-Hong Chen <i>O</i>-Aminoalkyl-<i>O</i>-Trimethyl-2,3-Dehydrosilybins: Synthesis and In Vitro Effects Towards Prostate Cancer Cells Molecules silybin prostate cancer 2,3-dehydrosilybin cell proliferation cell apoptosis |
| title | <i>O</i>-Aminoalkyl-<i>O</i>-Trimethyl-2,3-Dehydrosilybins: Synthesis and In Vitro Effects Towards Prostate Cancer Cells |
| title_full | <i>O</i>-Aminoalkyl-<i>O</i>-Trimethyl-2,3-Dehydrosilybins: Synthesis and In Vitro Effects Towards Prostate Cancer Cells |
| title_fullStr | <i>O</i>-Aminoalkyl-<i>O</i>-Trimethyl-2,3-Dehydrosilybins: Synthesis and In Vitro Effects Towards Prostate Cancer Cells |
| title_full_unstemmed | <i>O</i>-Aminoalkyl-<i>O</i>-Trimethyl-2,3-Dehydrosilybins: Synthesis and In Vitro Effects Towards Prostate Cancer Cells |
| title_short | <i>O</i>-Aminoalkyl-<i>O</i>-Trimethyl-2,3-Dehydrosilybins: Synthesis and In Vitro Effects Towards Prostate Cancer Cells |
| title_sort | i o i aminoalkyl i o i trimethyl 2 3 dehydrosilybins synthesis and in vitro effects towards prostate cancer cells |
| topic | silybin prostate cancer 2,3-dehydrosilybin cell proliferation cell apoptosis |
| url | https://www.mdpi.com/1420-3049/23/12/3142 |
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