TXNIP inhibition in the treatment of type 2 diabetes mellitus: design, synthesis, and biological evaluation of quinazoline derivatives
Thioredoxin interacting protein (TXNIP) is a potential drug target for type 2 diabetes mellitus (T2DM) treatment. A series of quinazoline derivatives were designed, synthesised, and evaluated to inhibit TXNIP expression and protect from palmitate (PA)-induced β cell injury. In vitro cell viability a...
| Main Authors: | , , , , , , , , |
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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/10.1080/14756366.2023.2166937 |
| _version_ | 1827123351822270464 |
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| author | Aiyun Li Li Guan Wanzhen Su Ning Zhao Xuwen Song Jin Wang Xiaoxiao Tang Weize Li Xiangying Jiao |
| author_facet | Aiyun Li Li Guan Wanzhen Su Ning Zhao Xuwen Song Jin Wang Xiaoxiao Tang Weize Li Xiangying Jiao |
| author_sort | Aiyun Li |
| collection | DOAJ |
| description | Thioredoxin interacting protein (TXNIP) is a potential drug target for type 2 diabetes mellitus (T2DM) treatment. A series of quinazoline derivatives were designed, synthesised, and evaluated to inhibit TXNIP expression and protect from palmitate (PA)-induced β cell injury. In vitro cell viability assay showed that compounds D-2 and C-1 could effectively protect β cell from PA-induced apoptosis, and subsequent results showed that these two compounds decreased TXNIP expression by accelerating its protein degradation. Mechanistically, compounds D-2 and C-1 reduced intracellular reactive oxygen species (ROS) production and modulated TXNIP-NLRP3 inflammasome signalling, and thus alleviating oxidative stress injury and inflammatory response under PA insult. Besides, these two compounds were predicted to possess better drug-likeness properties using SwissADME. The present study showed that compounds D-2 and C-1, especially compound D-2, were potent pancreatic β cell protective agents to inhibit TXNIP expression and might serve as promising lead candidates for the treatment of T2DM. |
| first_indexed | 2024-03-09T02:02:55Z |
| format | Article |
| id | doaj.art-7d2453d779634f62bc3e69e2165b917b |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2025-03-20T14:23:33Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-7d2453d779634f62bc3e69e2165b917b2024-09-09T17:23:19ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742023-12-0138110.1080/14756366.2023.2166937TXNIP inhibition in the treatment of type 2 diabetes mellitus: design, synthesis, and biological evaluation of quinazoline derivativesAiyun Li0Li Guan1Wanzhen Su2Ning Zhao3Xuwen Song4Jin Wang5Xiaoxiao Tang6Weize Li7Xiangying Jiao8Key Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education, and the Department of Physiology, Shanxi Medical University, Taiyuan, PR ChinaCollege of Pharmacy, Xi’an Medical University, Xi’an, PR ChinaKey Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education, and the Department of Physiology, Shanxi Medical University, Taiyuan, PR ChinaCollege of Pharmacy, Xi’an Medical University, Xi’an, PR ChinaCollege of Pharmacy, Xi’an Medical University, Xi’an, PR ChinaKey Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education, and the Department of Physiology, Shanxi Medical University, Taiyuan, PR ChinaCollege of Pharmacy, Xi’an Medical University, Xi’an, PR ChinaCollege of Pharmacy, Xi’an Medical University, Xi’an, PR ChinaKey Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education, and the Department of Physiology, Shanxi Medical University, Taiyuan, PR ChinaThioredoxin interacting protein (TXNIP) is a potential drug target for type 2 diabetes mellitus (T2DM) treatment. A series of quinazoline derivatives were designed, synthesised, and evaluated to inhibit TXNIP expression and protect from palmitate (PA)-induced β cell injury. In vitro cell viability assay showed that compounds D-2 and C-1 could effectively protect β cell from PA-induced apoptosis, and subsequent results showed that these two compounds decreased TXNIP expression by accelerating its protein degradation. Mechanistically, compounds D-2 and C-1 reduced intracellular reactive oxygen species (ROS) production and modulated TXNIP-NLRP3 inflammasome signalling, and thus alleviating oxidative stress injury and inflammatory response under PA insult. Besides, these two compounds were predicted to possess better drug-likeness properties using SwissADME. The present study showed that compounds D-2 and C-1, especially compound D-2, were potent pancreatic β cell protective agents to inhibit TXNIP expression and might serve as promising lead candidates for the treatment of T2DM.https://www.tandfonline.com/doi/10.1080/14756366.2023.2166937Quinazoline derivativesTXNIP inhibitionoxidative stress and inflammationpancreatic β cell apoptosisT2DM |
| spellingShingle | Aiyun Li Li Guan Wanzhen Su Ning Zhao Xuwen Song Jin Wang Xiaoxiao Tang Weize Li Xiangying Jiao TXNIP inhibition in the treatment of type 2 diabetes mellitus: design, synthesis, and biological evaluation of quinazoline derivatives Journal of Enzyme Inhibition and Medicinal Chemistry Quinazoline derivatives TXNIP inhibition oxidative stress and inflammation pancreatic β cell apoptosis T2DM |
| title | TXNIP inhibition in the treatment of type 2 diabetes mellitus: design, synthesis, and biological evaluation of quinazoline derivatives |
| title_full | TXNIP inhibition in the treatment of type 2 diabetes mellitus: design, synthesis, and biological evaluation of quinazoline derivatives |
| title_fullStr | TXNIP inhibition in the treatment of type 2 diabetes mellitus: design, synthesis, and biological evaluation of quinazoline derivatives |
| title_full_unstemmed | TXNIP inhibition in the treatment of type 2 diabetes mellitus: design, synthesis, and biological evaluation of quinazoline derivatives |
| title_short | TXNIP inhibition in the treatment of type 2 diabetes mellitus: design, synthesis, and biological evaluation of quinazoline derivatives |
| title_sort | txnip inhibition in the treatment of type 2 diabetes mellitus design synthesis and biological evaluation of quinazoline derivatives |
| topic | Quinazoline derivatives TXNIP inhibition oxidative stress and inflammation pancreatic β cell apoptosis T2DM |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2023.2166937 |
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