Design, synthesis and biological evaluation of 1-Aryl-5-(4-arylpiperazine-1-carbonyl)-1H-tetrazols as novel microtubule destabilizers
A series of 1-aryl-5-(4-arylpiperazine-1-carbonyl)-1H-tetrazols as microtubule destabilizers were designed, synthesised and evaluated for anticancer activity. Based on bioisosterism, we introduced the tetrazole moiety containing the hydrogen-bond acceptors as B-ring of XRP44X analogues. The key inte...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2021-01-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/14756366.2020.1759582 |
| _version_ | 1818332479664160768 |
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| author | Chao Wang Yuelin Li Zi Liu Zeyu Wang Zihan Liu Shuai Man Yujing Zhang Kai Bao Yingliang Wu Qi Guan Daiying Zuo Weige Zhang |
| author_facet | Chao Wang Yuelin Li Zi Liu Zeyu Wang Zihan Liu Shuai Man Yujing Zhang Kai Bao Yingliang Wu Qi Guan Daiying Zuo Weige Zhang |
| author_sort | Chao Wang |
| collection | DOAJ |
| description | A series of 1-aryl-5-(4-arylpiperazine-1-carbonyl)-1H-tetrazols as microtubule destabilizers were designed, synthesised and evaluated for anticancer activity. Based on bioisosterism, we introduced the tetrazole moiety containing the hydrogen-bond acceptors as B-ring of XRP44X analogues. The key intermediates ethyl 1-aryl-1H-tetrazole-5-carboxylates 10 can be simply and efficiently prepared via a microwave-assisted continuous operation process. Among the compounds synthesised, compound 6–31 showed noteworthy potency against SGC-7901, A549 and HeLa cell lines. In mechanism studies, compound 6–31 inhibited tubulin polymerisation and disorganised microtubule in SGC-7901 cells by binding to tubulin. Moreover, compound 6–31 arrested SGC-7901cells in G2/M phase. This study provided a new perspective for development of antitumor agents that target tubulin. |
| first_indexed | 2024-12-13T13:36:24Z |
| format | Article |
| id | doaj.art-1b1575218cb449939a32c6f200cd2555 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-12-13T13:36:24Z |
| publishDate | 2021-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-1b1575218cb449939a32c6f200cd25552022-12-21T23:43:47ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742021-01-0136154956010.1080/14756366.2020.17595821759582Design, synthesis and biological evaluation of 1-Aryl-5-(4-arylpiperazine-1-carbonyl)-1H-tetrazols as novel microtubule destabilizersChao Wang0Yuelin Li1Zi Liu2Zeyu Wang3Zihan Liu4Shuai Man5Yujing Zhang6Kai Bao7Yingliang Wu8Qi Guan9Daiying Zuo10Weige Zhang11Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical UniversityKey Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical UniversityDepartment of Pharmacology, Shenyang Pharmaceutical UniversityWuya College of Innovation, Shenyang Pharmaceutical UniversityKey Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical UniversityDepartment of Pharmacology, Shenyang Pharmaceutical UniversityKey Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical UniversityWuya College of Innovation, Shenyang Pharmaceutical UniversityDepartment of Pharmacology, Shenyang Pharmaceutical UniversityKey Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical UniversityDepartment of Pharmacology, Shenyang Pharmaceutical UniversityKey Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical UniversityA series of 1-aryl-5-(4-arylpiperazine-1-carbonyl)-1H-tetrazols as microtubule destabilizers were designed, synthesised and evaluated for anticancer activity. Based on bioisosterism, we introduced the tetrazole moiety containing the hydrogen-bond acceptors as B-ring of XRP44X analogues. The key intermediates ethyl 1-aryl-1H-tetrazole-5-carboxylates 10 can be simply and efficiently prepared via a microwave-assisted continuous operation process. Among the compounds synthesised, compound 6–31 showed noteworthy potency against SGC-7901, A549 and HeLa cell lines. In mechanism studies, compound 6–31 inhibited tubulin polymerisation and disorganised microtubule in SGC-7901 cells by binding to tubulin. Moreover, compound 6–31 arrested SGC-7901cells in G2/M phase. This study provided a new perspective for development of antitumor agents that target tubulin.http://dx.doi.org/10.1080/14756366.2020.1759582tetrazolemicrowaveantiproliferative activitymicrotubule destabilizermolecular docking |
| spellingShingle | Chao Wang Yuelin Li Zi Liu Zeyu Wang Zihan Liu Shuai Man Yujing Zhang Kai Bao Yingliang Wu Qi Guan Daiying Zuo Weige Zhang Design, synthesis and biological evaluation of 1-Aryl-5-(4-arylpiperazine-1-carbonyl)-1H-tetrazols as novel microtubule destabilizers Journal of Enzyme Inhibition and Medicinal Chemistry tetrazole microwave antiproliferative activity microtubule destabilizer molecular docking |
| title | Design, synthesis and biological evaluation of 1-Aryl-5-(4-arylpiperazine-1-carbonyl)-1H-tetrazols as novel microtubule destabilizers |
| title_full | Design, synthesis and biological evaluation of 1-Aryl-5-(4-arylpiperazine-1-carbonyl)-1H-tetrazols as novel microtubule destabilizers |
| title_fullStr | Design, synthesis and biological evaluation of 1-Aryl-5-(4-arylpiperazine-1-carbonyl)-1H-tetrazols as novel microtubule destabilizers |
| title_full_unstemmed | Design, synthesis and biological evaluation of 1-Aryl-5-(4-arylpiperazine-1-carbonyl)-1H-tetrazols as novel microtubule destabilizers |
| title_short | Design, synthesis and biological evaluation of 1-Aryl-5-(4-arylpiperazine-1-carbonyl)-1H-tetrazols as novel microtubule destabilizers |
| title_sort | design synthesis and biological evaluation of 1 aryl 5 4 arylpiperazine 1 carbonyl 1h tetrazols as novel microtubule destabilizers |
| topic | tetrazole microwave antiproliferative activity microtubule destabilizer molecular docking |
| url | http://dx.doi.org/10.1080/14756366.2020.1759582 |
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