Structural Optimization and Structure–Activity Relationship of 4-Thiazolidinone Derivatives as Novel Inhibitors of Human Dihydroorotate Dehydrogenase
Human dihydroorotate dehydrogenase (<i>h</i>DHODH), one of the attractive targets for the development of immunosuppressive drugs, is also a potential target of anticancer drugs and anti-leukemic drugs. The development of promising <i>h</i>DHODH inhibitors is in high demand. B...
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MDPI AG
2019-07-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/24/15/2780 |
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| author | Fanxun Zeng Lina Quan Guantian Yang Tiantian Qi Letian Zhang Shiliang Li Honglin Li Lili Zhu Xiaoyong Xu |
| author_facet | Fanxun Zeng Lina Quan Guantian Yang Tiantian Qi Letian Zhang Shiliang Li Honglin Li Lili Zhu Xiaoyong Xu |
| author_sort | Fanxun Zeng |
| collection | DOAJ |
| description | Human dihydroorotate dehydrogenase (<i>h</i>DHODH), one of the attractive targets for the development of immunosuppressive drugs, is also a potential target of anticancer drugs and anti-leukemic drugs. The development of promising <i>h</i>DHODH inhibitors is in high demand. Based on the unique binding mode of our previous reported 4-thiazolidinone derivatives, via molecular docking method, three new series 4-thiazolidinone derivatives were designed and synthesized as <i>h</i>DHODH inhibitors. The preliminary structure−activity relationship was investigated. Compound <b>9</b> of biphenyl series and compound <b>37</b> of amide series displayed IC<sub>50</sub> values of 1.32 μM and 1.45 μM, respectively. This research will provide valuable reference for the research of new structures of <i>h</i>DHODH inhibitors. |
| first_indexed | 2024-12-17T07:27:47Z |
| format | Article |
| id | doaj.art-8adda34c8bcb4efeac415607f2f04582 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-17T07:27:47Z |
| publishDate | 2019-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-8adda34c8bcb4efeac415607f2f045822022-12-21T21:58:34ZengMDPI AGMolecules1420-30492019-07-012415278010.3390/molecules24152780molecules24152780Structural Optimization and Structure–Activity Relationship of 4-Thiazolidinone Derivatives as Novel Inhibitors of Human Dihydroorotate DehydrogenaseFanxun Zeng0Lina Quan1Guantian Yang2Tiantian Qi3Letian Zhang4Shiliang Li5Honglin Li6Lili Zhu7Xiaoyong Xu8Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, ChinaShanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, ChinaShanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, ChinaShanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, ChinaShanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, ChinaShanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, ChinaShanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, ChinaShanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, ChinaShanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, ChinaHuman dihydroorotate dehydrogenase (<i>h</i>DHODH), one of the attractive targets for the development of immunosuppressive drugs, is also a potential target of anticancer drugs and anti-leukemic drugs. The development of promising <i>h</i>DHODH inhibitors is in high demand. Based on the unique binding mode of our previous reported 4-thiazolidinone derivatives, via molecular docking method, three new series 4-thiazolidinone derivatives were designed and synthesized as <i>h</i>DHODH inhibitors. The preliminary structure−activity relationship was investigated. Compound <b>9</b> of biphenyl series and compound <b>37</b> of amide series displayed IC<sub>50</sub> values of 1.32 μM and 1.45 μM, respectively. This research will provide valuable reference for the research of new structures of <i>h</i>DHODH inhibitors.https://www.mdpi.com/1420-3049/24/15/2780<i>h</i>DHODH inhibitorsstructural optimizationstructure–activity relationship4-thiazolidinones |
| spellingShingle | Fanxun Zeng Lina Quan Guantian Yang Tiantian Qi Letian Zhang Shiliang Li Honglin Li Lili Zhu Xiaoyong Xu Structural Optimization and Structure–Activity Relationship of 4-Thiazolidinone Derivatives as Novel Inhibitors of Human Dihydroorotate Dehydrogenase Molecules <i>h</i>DHODH inhibitors structural optimization structure–activity relationship 4-thiazolidinones |
| title | Structural Optimization and Structure–Activity Relationship of 4-Thiazolidinone Derivatives as Novel Inhibitors of Human Dihydroorotate Dehydrogenase |
| title_full | Structural Optimization and Structure–Activity Relationship of 4-Thiazolidinone Derivatives as Novel Inhibitors of Human Dihydroorotate Dehydrogenase |
| title_fullStr | Structural Optimization and Structure–Activity Relationship of 4-Thiazolidinone Derivatives as Novel Inhibitors of Human Dihydroorotate Dehydrogenase |
| title_full_unstemmed | Structural Optimization and Structure–Activity Relationship of 4-Thiazolidinone Derivatives as Novel Inhibitors of Human Dihydroorotate Dehydrogenase |
| title_short | Structural Optimization and Structure–Activity Relationship of 4-Thiazolidinone Derivatives as Novel Inhibitors of Human Dihydroorotate Dehydrogenase |
| title_sort | structural optimization and structure activity relationship of 4 thiazolidinone derivatives as novel inhibitors of human dihydroorotate dehydrogenase |
| topic | <i>h</i>DHODH inhibitors structural optimization structure–activity relationship 4-thiazolidinones |
| url | https://www.mdpi.com/1420-3049/24/15/2780 |
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