Design, synthesis and biological evaluation of 9-aryl-5H-pyrido[4,3-b]indole derivatives as potential tubulin polymerization inhibitors
A series of new 9-aryl-5H-pyrido[4,3-b]indole derivatives as tubulin polymerization inhibitors were designed, synthesized, and evaluated for antitumor activity. All newly prepared compounds were tested for their anti-proliferative activity in vitro against three different cancer cells (SGC-7901, HeL...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Chemistry |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2022.1004835/full |
| _version_ | 1828144749900464128 |
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| author | Lingyu Shi Lingyu Shi Shanbo Yang Shanbo Yang Jing Chang Jing Chang Yujing Zhang Wenjing Liu Wenjing Liu Jun Zeng Jun Zeng Jingsen Meng Jingsen Meng Renshuai Zhang Renshuai Zhang Chao Wang Chao Wang Dongming Xing Dongming Xing Dongming Xing |
| author_facet | Lingyu Shi Lingyu Shi Shanbo Yang Shanbo Yang Jing Chang Jing Chang Yujing Zhang Wenjing Liu Wenjing Liu Jun Zeng Jun Zeng Jingsen Meng Jingsen Meng Renshuai Zhang Renshuai Zhang Chao Wang Chao Wang Dongming Xing Dongming Xing Dongming Xing |
| author_sort | Lingyu Shi |
| collection | DOAJ |
| description | A series of new 9-aryl-5H-pyrido[4,3-b]indole derivatives as tubulin polymerization inhibitors were designed, synthesized, and evaluated for antitumor activity. All newly prepared compounds were tested for their anti-proliferative activity in vitro against three different cancer cells (SGC-7901, HeLa, and MCF-7). Among the designed compounds, compound 7k displayed the strongest anti-proliferative activity against HeLa cells with IC50 values of 8.7 ± 1.3 μM. In addition, 7k could inhibit the polymerization of tubulin and disrupt the microtubule network of cells. Further mechanism studies revealed that 7k arrested cell cycle at the G2/M phase and induced apoptosis in a dose-dependent manner. Molecular docking analysis confirmed that 7k may bind to colchicine binding sites on microtubules. Our study aims to provide a new strategy for the development of antitumor drugs targeting tubulin. |
| first_indexed | 2024-04-11T20:21:38Z |
| format | Article |
| id | doaj.art-75d388630e1849218b5b1c44a0951196 |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-04-11T20:21:38Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-75d388630e1849218b5b1c44a09511962022-12-22T04:04:48ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462022-09-011010.3389/fchem.2022.10048351004835Design, synthesis and biological evaluation of 9-aryl-5H-pyrido[4,3-b]indole derivatives as potential tubulin polymerization inhibitorsLingyu Shi0Lingyu Shi1Shanbo Yang2Shanbo Yang3Jing Chang4Jing Chang5Yujing Zhang6Wenjing Liu7Wenjing Liu8Jun Zeng9Jun Zeng10Jingsen Meng11Jingsen Meng12Renshuai Zhang13Renshuai Zhang14Chao Wang15Chao Wang16Dongming Xing17Dongming Xing18Dongming Xing19Cancer Institute, The Affiliated Hospital of Qingdao University and School of Basic Medicine, Qingdao University, Qingdao, ChinaQingdao Cancer Institute, Qingdao, ChinaCancer Institute, The Affiliated Hospital of Qingdao University and School of Basic Medicine, Qingdao University, Qingdao, ChinaQingdao Cancer Institute, Qingdao, ChinaCancer Institute, The Affiliated Hospital of Qingdao University and School of Basic Medicine, Qingdao University, Qingdao, ChinaQingdao Cancer Institute, Qingdao, ChinaThe Affiliated Cardiovascular Hospital of Qingdao University, Qingdao University, Qingdao, ChinaCancer Institute, The Affiliated Hospital of Qingdao University and School of Basic Medicine, Qingdao University, Qingdao, ChinaQingdao Cancer Institute, Qingdao, ChinaCancer Institute, The Affiliated Hospital of Qingdao University and School of Basic Medicine, Qingdao University, Qingdao, ChinaQingdao Cancer Institute, Qingdao, ChinaCancer Institute, The Affiliated Hospital of Qingdao University and School of Basic Medicine, Qingdao University, Qingdao, ChinaQingdao Cancer Institute, Qingdao, ChinaCancer Institute, The Affiliated Hospital of Qingdao University and School of Basic Medicine, Qingdao University, Qingdao, ChinaQingdao Cancer Institute, Qingdao, ChinaCancer Institute, The Affiliated Hospital of Qingdao University and School of Basic Medicine, Qingdao University, Qingdao, ChinaQingdao Cancer Institute, Qingdao, ChinaCancer Institute, The Affiliated Hospital of Qingdao University and School of Basic Medicine, Qingdao University, Qingdao, ChinaQingdao Cancer Institute, Qingdao, ChinaSchool of Life Sciences, Tsinghua University, Beijing, ChinaA series of new 9-aryl-5H-pyrido[4,3-b]indole derivatives as tubulin polymerization inhibitors were designed, synthesized, and evaluated for antitumor activity. All newly prepared compounds were tested for their anti-proliferative activity in vitro against three different cancer cells (SGC-7901, HeLa, and MCF-7). Among the designed compounds, compound 7k displayed the strongest anti-proliferative activity against HeLa cells with IC50 values of 8.7 ± 1.3 μM. In addition, 7k could inhibit the polymerization of tubulin and disrupt the microtubule network of cells. Further mechanism studies revealed that 7k arrested cell cycle at the G2/M phase and induced apoptosis in a dose-dependent manner. Molecular docking analysis confirmed that 7k may bind to colchicine binding sites on microtubules. Our study aims to provide a new strategy for the development of antitumor drugs targeting tubulin.https://www.frontiersin.org/articles/10.3389/fchem.2022.1004835/fulltubulinpyrido[4,3-b]indoleantitumor activitymolecular dockingtubulin polymerization inhibitors |
| spellingShingle | Lingyu Shi Lingyu Shi Shanbo Yang Shanbo Yang Jing Chang Jing Chang Yujing Zhang Wenjing Liu Wenjing Liu Jun Zeng Jun Zeng Jingsen Meng Jingsen Meng Renshuai Zhang Renshuai Zhang Chao Wang Chao Wang Dongming Xing Dongming Xing Dongming Xing Design, synthesis and biological evaluation of 9-aryl-5H-pyrido[4,3-b]indole derivatives as potential tubulin polymerization inhibitors Frontiers in Chemistry tubulin pyrido[4,3-b]indole antitumor activity molecular docking tubulin polymerization inhibitors |
| title | Design, synthesis and biological evaluation of 9-aryl-5H-pyrido[4,3-b]indole derivatives as potential tubulin polymerization inhibitors |
| title_full | Design, synthesis and biological evaluation of 9-aryl-5H-pyrido[4,3-b]indole derivatives as potential tubulin polymerization inhibitors |
| title_fullStr | Design, synthesis and biological evaluation of 9-aryl-5H-pyrido[4,3-b]indole derivatives as potential tubulin polymerization inhibitors |
| title_full_unstemmed | Design, synthesis and biological evaluation of 9-aryl-5H-pyrido[4,3-b]indole derivatives as potential tubulin polymerization inhibitors |
| title_short | Design, synthesis and biological evaluation of 9-aryl-5H-pyrido[4,3-b]indole derivatives as potential tubulin polymerization inhibitors |
| title_sort | design synthesis and biological evaluation of 9 aryl 5h pyrido 4 3 b indole derivatives as potential tubulin polymerization inhibitors |
| topic | tubulin pyrido[4,3-b]indole antitumor activity molecular docking tubulin polymerization inhibitors |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2022.1004835/full |
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