Discovery a series of novel inhibitors of human dihydroorotate dehydrogenase : Biological activity evaluation and molecular docking
© 2023 John Wiley & Sons A/S..
Human dihydroorotate dehydrogenase (hDHODH) is a key enzyme that catalyzes the de novo synthesis of pyrimidine. In recent years, various studies have shown that inhibiting this enzyme can treat autoimmune diseases such as rheumatoid arthritis (RA) and cancer. This study designed and synthesized a series of novel thiazolidone hDHODH inhibitors. Through biological activity evaluation, Compound 14 was found to have high inhibitory activity, with an IC50 value reaching nanomolar level. Preliminary structure-activity relationship studies found that the carboxyl group in R1 and the naphthalene in R2 are key factors in improving activity. Through molecular docking, the binding mode between inhibitors and proteins was elucidated. This study provides an important reference for further optimizing hDHODH inhibitors.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:103 |
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| Enthalten in: |
Chemical biology & drug design - 103(2024), 1 vom: 21. Jan., Seite e14388 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ren, Xiaoli [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 18.01.2024 Date Revised 25.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/cbdd.14388 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM364183969 |
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| 245 | 1 | 0 | |a Discovery a series of novel inhibitors of human dihydroorotate dehydrogenase |b Biological activity evaluation and molecular docking |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 John Wiley & Sons A/S. | ||
| 520 | |a Human dihydroorotate dehydrogenase (hDHODH) is a key enzyme that catalyzes the de novo synthesis of pyrimidine. In recent years, various studies have shown that inhibiting this enzyme can treat autoimmune diseases such as rheumatoid arthritis (RA) and cancer. This study designed and synthesized a series of novel thiazolidone hDHODH inhibitors. Through biological activity evaluation, Compound 14 was found to have high inhibitory activity, with an IC50 value reaching nanomolar level. Preliminary structure-activity relationship studies found that the carboxyl group in R1 and the naphthalene in R2 are key factors in improving activity. Through molecular docking, the binding mode between inhibitors and proteins was elucidated. This study provides an important reference for further optimizing hDHODH inhibitors | ||
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| 650 | 4 | |a molecular docking | |
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| 700 | 1 | |a Liu, Xiaoyong |e verfasserin |4 aut | |
| 700 | 1 | |a Hua, Miao |e verfasserin |4 aut | |
| 700 | 1 | |a Dai, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Ren, Xiaoping |e verfasserin |4 aut | |
| 700 | 1 | |a Sui, Chaoya |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xiangbi |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Zhiyong |e verfasserin |4 aut | |
| 700 | 1 | |a Tian, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Bing |e verfasserin |4 aut | |
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