Design, synthesis and biological evaluation of quinazoline and pyrrolo[3,2-d]pyrimidine derivatives as TLR7 agonists for antiviral agents
Pattern recognition receptors (PRRs) play a critical role in the innate immune response, and toll-like receptor 7 (TLR7) is an important member of PRRs. Although several TLR7 agonists are available, most of them are being tested clinically, with only one available on the market. Thus, it is imperative to develop new TLR7 agonists. In this study, we designed and synthesized three kinds of quinazoline derivatives and five kinds of pyrrolo[3,2-d]pyrimidine derivatives targeting TLR7. The antiviral efficacy of these compounds was evaluated in vitro and in vivo. Our findings indicated that four kinds of compounds showed exceptional antiviral activity. Furthermore, molecular docking studies confirmed that compound 11 successfully positioned itself in the pocket of the TLR7 guanosine loading site with a binding energy of -4.45 kcal mol-1. These results suggested that these compounds might be potential antiviral agents.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:22 |
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| Enthalten in: |
Organic & biomolecular chemistry - 22(2024), 14 vom: 03. Apr., Seite 2764-2773 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Song, Yue [VerfasserIn] |
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| Links: |
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| Themen: |
Adjuvants, Immunologic |
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| Anmerkungen: |
Date Completed 04.04.2024 Date Revised 04.04.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1039/d4ob00048j |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369868919 |
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| 245 | 1 | 0 | |a Design, synthesis and biological evaluation of quinazoline and pyrrolo[3,2-d]pyrimidine derivatives as TLR7 agonists for antiviral agents |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Pattern recognition receptors (PRRs) play a critical role in the innate immune response, and toll-like receptor 7 (TLR7) is an important member of PRRs. Although several TLR7 agonists are available, most of them are being tested clinically, with only one available on the market. Thus, it is imperative to develop new TLR7 agonists. In this study, we designed and synthesized three kinds of quinazoline derivatives and five kinds of pyrrolo[3,2-d]pyrimidine derivatives targeting TLR7. The antiviral efficacy of these compounds was evaluated in vitro and in vivo. Our findings indicated that four kinds of compounds showed exceptional antiviral activity. Furthermore, molecular docking studies confirmed that compound 11 successfully positioned itself in the pocket of the TLR7 guanosine loading site with a binding energy of -4.45 kcal mol-1. These results suggested that these compounds might be potential antiviral agents | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Toll-Like Receptor 7 |2 NLM | |
| 650 | 7 | |a Quinazolines |2 NLM | |
| 650 | 7 | |a Adjuvants, Immunologic |2 NLM | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 650 | 7 | |a Pyrimidines |2 NLM | |
| 700 | 1 | |a Fan, Wenjie |e verfasserin |4 aut | |
| 700 | 1 | |a Yao, Chen |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Heng |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Xiuxiang |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yumin |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Pengxiang |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Yanjie |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Zhen |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jiang |e verfasserin |4 aut | |
| 700 | 1 | |a Chu, BeiBei |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Lijun |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Guoyu |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Mengdi |e verfasserin |4 aut | |
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