Design, synthesis and antiviral evaluation of novel conjugates of the 1,7,7-trimethylbicyclo[2.2.1]heptane scaffold and saturated N-heterocycles via 1,2,3-triazole linker
© 2023 Deutsche Pharmazeutische Gesellschaft..
A new series of heterocyclic derivatives with a 1,7,7-trimethylbicyclo[2.2.1]heptane fragment was designed, synthesised and biologically evaluated. Synthesis of the target compounds was performed using the Cu(I) catalysed cycloaddition reaction. The key starting substances in the click reaction were an alkyne containing a 1,7,7-trimethylbicyclo[2.2.1]heptane fragment and a series of azides with saturated nitrogen-containing heterocycles. Some of the derivatives were found to exhibit strong antiviral activity against Marburg and Ebola pseudotype viruses. Lysosomal trapping assays revealed the derivatives to possess lysosomotropic properties. The molecular modelling study demonstrated the binding affinity between the compounds investigated and the possible active site to be mainly due to hydrophobic interactions. Thus, combining a natural hydrophobic structural fragment and a lysosome-targetable heterocycle may be an effective strategy for designing antiviral agents.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:357 |
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| Enthalten in: |
Archiv der Pharmazie - 357(2024), 3 vom: 29. März, Seite e2300549 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sokolova, Anastasiya S [VerfasserIn] |
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| Links: |
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| Themen: |
Antiviral Agents |
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| Anmerkungen: |
Date Completed 04.03.2024 Date Revised 04.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/ardp.202300549 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 245 | 1 | 0 | |a Design, synthesis and antiviral evaluation of novel conjugates of the 1,7,7-trimethylbicyclo[2.2.1]heptane scaffold and saturated N-heterocycles via 1,2,3-triazole linker |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 Deutsche Pharmazeutische Gesellschaft. | ||
| 520 | |a A new series of heterocyclic derivatives with a 1,7,7-trimethylbicyclo[2.2.1]heptane fragment was designed, synthesised and biologically evaluated. Synthesis of the target compounds was performed using the Cu(I) catalysed cycloaddition reaction. The key starting substances in the click reaction were an alkyne containing a 1,7,7-trimethylbicyclo[2.2.1]heptane fragment and a series of azides with saturated nitrogen-containing heterocycles. Some of the derivatives were found to exhibit strong antiviral activity against Marburg and Ebola pseudotype viruses. Lysosomal trapping assays revealed the derivatives to possess lysosomotropic properties. The molecular modelling study demonstrated the binding affinity between the compounds investigated and the possible active site to be mainly due to hydrophobic interactions. Thus, combining a natural hydrophobic structural fragment and a lysosome-targetable heterocycle may be an effective strategy for designing antiviral agents | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a lysosomotropic compounds | |
| 650 | 4 | |a monoterpenoids derivatives | |
| 650 | 4 | |a virus inhibitors | |
| 650 | 7 | |a Heptanes |2 NLM | |
| 650 | 7 | |a Triazoles |2 NLM | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 700 | 1 | |a Yarovaya, Olga I |e verfasserin |4 aut | |
| 700 | 1 | |a Artyushin, Oleg I |e verfasserin |4 aut | |
| 700 | 1 | |a Sharova, Elena V |e verfasserin |4 aut | |
| 700 | 1 | |a Baev, Dmitriy S |e verfasserin |4 aut | |
| 700 | 1 | |a Mordvinova, Ekaterina D |e verfasserin |4 aut | |
| 700 | 1 | |a Shcherbakov, Dmitriy N |e verfasserin |4 aut | |
| 700 | 1 | |a Shnaider, Tatiana A |e verfasserin |4 aut | |
| 700 | 1 | |a Nikitina, Tatiana V |e verfasserin |4 aut | |
| 700 | 1 | |a Esaulkova, Iana L |e verfasserin |4 aut | |
| 700 | 1 | |a Ilyina, Polina A |e verfasserin |4 aut | |
| 700 | 1 | |a Zarubaev, Vladimir V |e verfasserin |4 aut | |
| 700 | 1 | |a Brel, Valery K |e verfasserin |4 aut | |
| 700 | 1 | |a Tolstikova, Tatyana G |e verfasserin |4 aut | |
| 700 | 1 | |a Salakhutdinov, Nariman F |e verfasserin |4 aut | |
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