Synthesis and antitumor activity of litseaone B analogues as tubulin polymerisation inhibitors
A series of litseaone B analogues 4a∼4p were synthesised and antitumor activities of all compounds were screened. These compounds were designed by introducing different substituents on the B ring. Among these synthesised compounds, it was proved that 4k showed excellent activity against A549, HepG2,...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2022.2122962 |
| _version_ | 1798033333039398912 |
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| author | Wei Yang Huining Peng Yong Huang Zhiyun Peng Guangcheng Wang |
| author_facet | Wei Yang Huining Peng Yong Huang Zhiyun Peng Guangcheng Wang |
| author_sort | Wei Yang |
| collection | DOAJ |
| description | A series of litseaone B analogues 4a∼4p were synthesised and antitumor activities of all compounds were screened. These compounds were designed by introducing different substituents on the B ring. Among these synthesised compounds, it was proved that 4k showed excellent activity against A549, HepG2, and HCT-15 cell lines, the IC50 values were 7.60 μM, 20.53 μM, and 4.59 μM, respectively. The results of tubulin polymerisation inhibition and immunofluorescence staining experiments displayed that 4k could act on tubulin and inhibit the polymerisation of tubulin. Moreover, the wound healing assay showed that 4k could inhibit the migration of A549 cells in a dose-dependent manner. Furthermore, the results of flow cytometry revealed that 4k was capable of blocking the cell cycle in the G2/M phase, inducing a decrease in the mitochondrial membrane potential and ultimately leading to apoptosis in A549 cells. Importantly, the possible binding model was also performed by molecular docking. Subject classification codes: short communication. |
| first_indexed | 2024-04-11T20:27:35Z |
| format | Article |
| id | doaj.art-dc74d280d4c24f3f97031f213a7b1caf |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-04-11T20:27:35Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-dc74d280d4c24f3f97031f213a7b1caf2022-12-22T04:04:36ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742022-12-013712530253910.1080/14756366.2022.2122962Synthesis and antitumor activity of litseaone B analogues as tubulin polymerisation inhibitorsWei Yang0Huining Peng1Yong Huang2Zhiyun Peng3Guangcheng Wang4State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, ChinaState Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, ChinaEngineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Medical University, Guiyang, ChinaClinical Trails Center, The Affiliated Hospital of Guizhou Medical University, Guiyang, ChinaState Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, ChinaA series of litseaone B analogues 4a∼4p were synthesised and antitumor activities of all compounds were screened. These compounds were designed by introducing different substituents on the B ring. Among these synthesised compounds, it was proved that 4k showed excellent activity against A549, HepG2, and HCT-15 cell lines, the IC50 values were 7.60 μM, 20.53 μM, and 4.59 μM, respectively. The results of tubulin polymerisation inhibition and immunofluorescence staining experiments displayed that 4k could act on tubulin and inhibit the polymerisation of tubulin. Moreover, the wound healing assay showed that 4k could inhibit the migration of A549 cells in a dose-dependent manner. Furthermore, the results of flow cytometry revealed that 4k was capable of blocking the cell cycle in the G2/M phase, inducing a decrease in the mitochondrial membrane potential and ultimately leading to apoptosis in A549 cells. Importantly, the possible binding model was also performed by molecular docking. Subject classification codes: short communication.https://www.tandfonline.com/doi/10.1080/14756366.2022.2122962Litseaone Btubulin polymerisation inhibitorsanticancer |
| spellingShingle | Wei Yang Huining Peng Yong Huang Zhiyun Peng Guangcheng Wang Synthesis and antitumor activity of litseaone B analogues as tubulin polymerisation inhibitors Journal of Enzyme Inhibition and Medicinal Chemistry Litseaone B tubulin polymerisation inhibitors anticancer |
| title | Synthesis and antitumor activity of litseaone B analogues as tubulin polymerisation inhibitors |
| title_full | Synthesis and antitumor activity of litseaone B analogues as tubulin polymerisation inhibitors |
| title_fullStr | Synthesis and antitumor activity of litseaone B analogues as tubulin polymerisation inhibitors |
| title_full_unstemmed | Synthesis and antitumor activity of litseaone B analogues as tubulin polymerisation inhibitors |
| title_short | Synthesis and antitumor activity of litseaone B analogues as tubulin polymerisation inhibitors |
| title_sort | synthesis and antitumor activity of litseaone b analogues as tubulin polymerisation inhibitors |
| topic | Litseaone B tubulin polymerisation inhibitors anticancer |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2022.2122962 |
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