Discovery of dual tubulin-NEDDylation inhibitors with antiproliferative activity
AbstractAlthough various dual-target tubulin inhibitors have been designed and synthesised, no dual tubulin-NEDDylation inhibitors as antiproliferative agents were reported so far. In this work, a series of trimethoxyphenyl analogues as potential dual tubulin-NEDDylation inhibitors were synthesised...
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2023-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2022.2136173 |
| _version_ | 1797400913232527360 |
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| author | Dong-Jun Fu Ting Wang |
| author_facet | Dong-Jun Fu Ting Wang |
| author_sort | Dong-Jun Fu |
| collection | DOAJ |
| description | AbstractAlthough various dual-target tubulin inhibitors have been designed and synthesised, no dual tubulin-NEDDylation inhibitors as antiproliferative agents were reported so far. In this work, a series of trimethoxyphenyl analogues as potential dual tubulin-NEDDylation inhibitors were synthesised and evaluated for their antiproliferative activity. Among them, compound C11 exhibited the most potent inhibitory activity with IC50 values of 1.17, 2.48, and 1.47 μM against HepG2, PC3, and MCF7 cells, respectively. In addition, it displayed the potent inhibitory activity against tubulin with an IC50 value of 2.40 μM and obviously inhibited tubulin polymerisation in HepG2 cells. Furthermore, C11 inhibited NEDDylation by a ATP-dependent manner. Molecular docking studies revealed that the methoxy group and dithiocarbamate group of C11 could form hydrogen bonds with residues of tubulin and E1 NEDD8-activating enzyme (NAE). These results suggested that compound C11 was a dual tubulin-NEDDylation inhibitor with antiproliferative activity. |
| first_indexed | 2024-03-09T02:02:23Z |
| format | Article |
| id | doaj.art-092f963dc7364177a1a573db49e0c446 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-03-09T02:02:23Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-092f963dc7364177a1a573db49e0c4462023-12-08T03:24:22ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742023-12-0138116617510.1080/14756366.2022.2136173Discovery of dual tubulin-NEDDylation inhibitors with antiproliferative activityDong-Jun Fu0Ting Wang1Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, ChinaBeijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, ChinaAbstractAlthough various dual-target tubulin inhibitors have been designed and synthesised, no dual tubulin-NEDDylation inhibitors as antiproliferative agents were reported so far. In this work, a series of trimethoxyphenyl analogues as potential dual tubulin-NEDDylation inhibitors were synthesised and evaluated for their antiproliferative activity. Among them, compound C11 exhibited the most potent inhibitory activity with IC50 values of 1.17, 2.48, and 1.47 μM against HepG2, PC3, and MCF7 cells, respectively. In addition, it displayed the potent inhibitory activity against tubulin with an IC50 value of 2.40 μM and obviously inhibited tubulin polymerisation in HepG2 cells. Furthermore, C11 inhibited NEDDylation by a ATP-dependent manner. Molecular docking studies revealed that the methoxy group and dithiocarbamate group of C11 could form hydrogen bonds with residues of tubulin and E1 NEDD8-activating enzyme (NAE). These results suggested that compound C11 was a dual tubulin-NEDDylation inhibitor with antiproliferative activity.https://www.tandfonline.com/doi/10.1080/14756366.2022.2136173TubulinNEDDylationmolecular dockingantiproliferative activity |
| spellingShingle | Dong-Jun Fu Ting Wang Discovery of dual tubulin-NEDDylation inhibitors with antiproliferative activity Journal of Enzyme Inhibition and Medicinal Chemistry Tubulin NEDDylation molecular docking antiproliferative activity |
| title | Discovery of dual tubulin-NEDDylation inhibitors with antiproliferative activity |
| title_full | Discovery of dual tubulin-NEDDylation inhibitors with antiproliferative activity |
| title_fullStr | Discovery of dual tubulin-NEDDylation inhibitors with antiproliferative activity |
| title_full_unstemmed | Discovery of dual tubulin-NEDDylation inhibitors with antiproliferative activity |
| title_short | Discovery of dual tubulin-NEDDylation inhibitors with antiproliferative activity |
| title_sort | discovery of dual tubulin neddylation inhibitors with antiproliferative activity |
| topic | Tubulin NEDDylation molecular docking antiproliferative activity |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2022.2136173 |
| work_keys_str_mv | AT dongjunfu discoveryofdualtubulinneddylationinhibitorswithantiproliferativeactivity AT tingwang discoveryofdualtubulinneddylationinhibitorswithantiproliferativeactivity |