Synthesis, Characterization and Biological Evaluation of Magnolol and Honokiol Derivatives with 1,3,5-Triazine of Metformin Cyclization
Herein, we sought to evaluate the contribution of the 1,3,5-triazine ring through the metformin cyclization unit to the biological activity of magnolol and honokiol-conjugates. One of the phenolic OH groups of magnolol or honokiol was replaced by a 1,3,5-triazine ring to further explore their synthe...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-12-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/25/24/5779 |
| _version_ | 1827700584395833344 |
|---|---|
| author | Cui Ren Juanxia Wang Youzhen Tan Mingxin Guo Jieqing Guo Ying Liu Xia Wu Yifan Feng |
| author_facet | Cui Ren Juanxia Wang Youzhen Tan Mingxin Guo Jieqing Guo Ying Liu Xia Wu Yifan Feng |
| author_sort | Cui Ren |
| collection | DOAJ |
| description | Herein, we sought to evaluate the contribution of the 1,3,5-triazine ring through the metformin cyclization unit to the biological activity of magnolol and honokiol-conjugates. One of the phenolic OH groups of magnolol or honokiol was replaced by a 1,3,5-triazine ring to further explore their synthesis and medicinal versatility. In this study, a robust procedure of three steps was adopted for the synthesis of magnolol and honokiol derivatives by alkylation of potassium carbonate with a 1,3,5-triazine ring. To our knowledge, this is the first report to connect one of the phenolic OH positions of magnolol or honokiol to a 1,3,5-triazine ring cyclized by metformin. The structural characterization of three new compounds was carried out via spectroscopic techniques, i.e., <sup>13</sup>C NMR, <sup>1</sup>H NMR, and HRMS. Surprisingly, these compounds showed no cytotoxicity against RAW 264.7 macrophages but significantly inhibited the proliferation of MCF-7 (human breast cancer cells), HepG2 (human hepatoma cells), A549 (human lung carcinoma cells), and BxPC-3 (human pancreatic carcinoma cells) tumor cell lines. Furthermore, the compounds also significantly inhibited the release of inflammatory cytokines, including nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in the lipopolysaccharide (LPS)-activated mouse cells (RAW 264.7). Among them, compound 2 demonstrated promising broad-spectrum antiproliferative potential with half inhibitory concentration (IC<sub>50</sub>) values ranging from 5.57 to 8.74 µM and it significantly decreased caspase-3 and Bcl-2 expression in HepG2 cells. These interesting findings show that derivatization of magnolol and honokiol with 1,3,5-triazine affects and modulates their biological properties. |
| first_indexed | 2024-03-10T14:16:05Z |
| format | Article |
| id | doaj.art-f2654e0ed1ff4f9491ceeb3c41a34c79 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T14:16:05Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-f2654e0ed1ff4f9491ceeb3c41a34c792023-11-20T23:49:56ZengMDPI AGMolecules1420-30492020-12-012524577910.3390/molecules25245779Synthesis, Characterization and Biological Evaluation of Magnolol and Honokiol Derivatives with 1,3,5-Triazine of Metformin CyclizationCui Ren0Juanxia Wang1Youzhen Tan2Mingxin Guo3Jieqing Guo4Ying Liu5Xia Wu6Yifan Feng7New Drug Research and Development Center, Guangdong Pharmaceutical University, Guangzhou 510006, ChinaNew Drug Research and Development Center, Guangdong Pharmaceutical University, Guangzhou 510006, ChinaNew Drug Research and Development Center, Guangdong Pharmaceutical University, Guangzhou 510006, ChinaNew Drug Research and Development Center, Guangdong Pharmaceutical University, Guangzhou 510006, ChinaNew Drug Research and Development Center, Guangdong Pharmaceutical University, Guangzhou 510006, ChinaNew Drug Research and Development Center, Guangdong Pharmaceutical University, Guangzhou 510006, ChinaNew Drug Research and Development Center, Guangdong Pharmaceutical University, Guangzhou 510006, ChinaNew Drug Research and Development Center, Guangdong Pharmaceutical University, Guangzhou 510006, ChinaHerein, we sought to evaluate the contribution of the 1,3,5-triazine ring through the metformin cyclization unit to the biological activity of magnolol and honokiol-conjugates. One of the phenolic OH groups of magnolol or honokiol was replaced by a 1,3,5-triazine ring to further explore their synthesis and medicinal versatility. In this study, a robust procedure of three steps was adopted for the synthesis of magnolol and honokiol derivatives by alkylation of potassium carbonate with a 1,3,5-triazine ring. To our knowledge, this is the first report to connect one of the phenolic OH positions of magnolol or honokiol to a 1,3,5-triazine ring cyclized by metformin. The structural characterization of three new compounds was carried out via spectroscopic techniques, i.e., <sup>13</sup>C NMR, <sup>1</sup>H NMR, and HRMS. Surprisingly, these compounds showed no cytotoxicity against RAW 264.7 macrophages but significantly inhibited the proliferation of MCF-7 (human breast cancer cells), HepG2 (human hepatoma cells), A549 (human lung carcinoma cells), and BxPC-3 (human pancreatic carcinoma cells) tumor cell lines. Furthermore, the compounds also significantly inhibited the release of inflammatory cytokines, including nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in the lipopolysaccharide (LPS)-activated mouse cells (RAW 264.7). Among them, compound 2 demonstrated promising broad-spectrum antiproliferative potential with half inhibitory concentration (IC<sub>50</sub>) values ranging from 5.57 to 8.74 µM and it significantly decreased caspase-3 and Bcl-2 expression in HepG2 cells. These interesting findings show that derivatization of magnolol and honokiol with 1,3,5-triazine affects and modulates their biological properties.https://www.mdpi.com/1420-3049/25/24/5779magnololhonokiolmetforminchemical synthesisbiological activity |
| spellingShingle | Cui Ren Juanxia Wang Youzhen Tan Mingxin Guo Jieqing Guo Ying Liu Xia Wu Yifan Feng Synthesis, Characterization and Biological Evaluation of Magnolol and Honokiol Derivatives with 1,3,5-Triazine of Metformin Cyclization Molecules magnolol honokiol metformin chemical synthesis biological activity |
| title | Synthesis, Characterization and Biological Evaluation of Magnolol and Honokiol Derivatives with 1,3,5-Triazine of Metformin Cyclization |
| title_full | Synthesis, Characterization and Biological Evaluation of Magnolol and Honokiol Derivatives with 1,3,5-Triazine of Metformin Cyclization |
| title_fullStr | Synthesis, Characterization and Biological Evaluation of Magnolol and Honokiol Derivatives with 1,3,5-Triazine of Metformin Cyclization |
| title_full_unstemmed | Synthesis, Characterization and Biological Evaluation of Magnolol and Honokiol Derivatives with 1,3,5-Triazine of Metformin Cyclization |
| title_short | Synthesis, Characterization and Biological Evaluation of Magnolol and Honokiol Derivatives with 1,3,5-Triazine of Metformin Cyclization |
| title_sort | synthesis characterization and biological evaluation of magnolol and honokiol derivatives with 1 3 5 triazine of metformin cyclization |
| topic | magnolol honokiol metformin chemical synthesis biological activity |
| url | https://www.mdpi.com/1420-3049/25/24/5779 |
| work_keys_str_mv | AT cuiren synthesischaracterizationandbiologicalevaluationofmagnololandhonokiolderivativeswith135triazineofmetformincyclization AT juanxiawang synthesischaracterizationandbiologicalevaluationofmagnololandhonokiolderivativeswith135triazineofmetformincyclization AT youzhentan synthesischaracterizationandbiologicalevaluationofmagnololandhonokiolderivativeswith135triazineofmetformincyclization AT mingxinguo synthesischaracterizationandbiologicalevaluationofmagnololandhonokiolderivativeswith135triazineofmetformincyclization AT jieqingguo synthesischaracterizationandbiologicalevaluationofmagnololandhonokiolderivativeswith135triazineofmetformincyclization AT yingliu synthesischaracterizationandbiologicalevaluationofmagnololandhonokiolderivativeswith135triazineofmetformincyclization AT xiawu synthesischaracterizationandbiologicalevaluationofmagnololandhonokiolderivativeswith135triazineofmetformincyclization AT yifanfeng synthesischaracterizationandbiologicalevaluationofmagnololandhonokiolderivativeswith135triazineofmetformincyclization |