3-(5-Hydroxyphenyl)-5-Phenyl-2-Pyrazolines as Toll-Like Receptor 7 Agonists
Toll-like receptor 7 (TLR7) is an attractive target for developing immune modulators to enhance innate immunity against ssRNA virus infections, including hepatitis C and COVID-19. Ten 3-(5-hydroxyphenyl)-5-phenyl-2-pyrazolines were tested using TLR7 reporter cells, overexpressing TLR7 and the NF-κB-...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-01-01
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| Series: | Journal of Chemistry |
| Online Access: | http://dx.doi.org/10.1155/2023/2151669 |
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| _version_ | 1832548009702850560 |
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| author | Ji Hwan Kim Seunghyun Ahn Dongsoo Koh Young Han Lee Yoongho Lim Soon Young Shin |
| author_facet | Ji Hwan Kim Seunghyun Ahn Dongsoo Koh Young Han Lee Yoongho Lim Soon Young Shin |
| author_sort | Ji Hwan Kim |
| collection | DOAJ |
| description | Toll-like receptor 7 (TLR7) is an attractive target for developing immune modulators to enhance innate immunity against ssRNA virus infections, including hepatitis C and COVID-19. Ten 3-(5-hydroxyphenyl)-5-phenyl-2-pyrazolines were tested using TLR7 reporter cells, overexpressing TLR7 and the NF-κB-inducible SEAP reporter gene to discover a novel TLR7 agonist enhancing innate immunity. Of these, 2-(3-(2-hydroxynaphthalen-1-yl)-5-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4(5H)-one (compound 6) showed the best TLR7 agonistic activity, and further experiments were carried out to study the immune-modulatory capability of compound 6. Treatment with compound 6 rapidly induced phosphorylation of IRAK4, IKKα/β, IκBα, and p65/RelA in THP1 monocytic cells. In addition, it increased the expression of NF-κB-regulated innate cytokines, such as TNFα and IL1β, in THP1 monocytic cells. These data suggest that compound 6 induces an innate immune response by agonizing TLR7 activity in THP1 human monocytic cells. Therefore, compound 6 can be used as an innate immune modulator to develop antiviral agents and vaccine adjuvants. |
| format | Article |
| id | doaj-art-bb06daeaea2c401f8b8f85d06363e156 |
| institution | Kabale University |
| issn | 2090-9071 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Chemistry |
| spelling | doaj-art-bb06daeaea2c401f8b8f85d06363e1562025-02-03T06:42:39ZengWileyJournal of Chemistry2090-90712023-01-01202310.1155/2023/21516693-(5-Hydroxyphenyl)-5-Phenyl-2-Pyrazolines as Toll-Like Receptor 7 AgonistsJi Hwan Kim0Seunghyun Ahn1Dongsoo Koh2Young Han Lee3Yoongho Lim4Soon Young Shin5Division of Bioscience and BiotechnologyDepartment of Applied ChemistryDepartment of Applied ChemistryDepartment of Biological SciencesDivision of Bioscience and BiotechnologyDepartment of Biological SciencesToll-like receptor 7 (TLR7) is an attractive target for developing immune modulators to enhance innate immunity against ssRNA virus infections, including hepatitis C and COVID-19. Ten 3-(5-hydroxyphenyl)-5-phenyl-2-pyrazolines were tested using TLR7 reporter cells, overexpressing TLR7 and the NF-κB-inducible SEAP reporter gene to discover a novel TLR7 agonist enhancing innate immunity. Of these, 2-(3-(2-hydroxynaphthalen-1-yl)-5-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4(5H)-one (compound 6) showed the best TLR7 agonistic activity, and further experiments were carried out to study the immune-modulatory capability of compound 6. Treatment with compound 6 rapidly induced phosphorylation of IRAK4, IKKα/β, IκBα, and p65/RelA in THP1 monocytic cells. In addition, it increased the expression of NF-κB-regulated innate cytokines, such as TNFα and IL1β, in THP1 monocytic cells. These data suggest that compound 6 induces an innate immune response by agonizing TLR7 activity in THP1 human monocytic cells. Therefore, compound 6 can be used as an innate immune modulator to develop antiviral agents and vaccine adjuvants.http://dx.doi.org/10.1155/2023/2151669 |
| spellingShingle | Ji Hwan Kim Seunghyun Ahn Dongsoo Koh Young Han Lee Yoongho Lim Soon Young Shin 3-(5-Hydroxyphenyl)-5-Phenyl-2-Pyrazolines as Toll-Like Receptor 7 Agonists Journal of Chemistry |
| title | 3-(5-Hydroxyphenyl)-5-Phenyl-2-Pyrazolines as Toll-Like Receptor 7 Agonists |
| title_full | 3-(5-Hydroxyphenyl)-5-Phenyl-2-Pyrazolines as Toll-Like Receptor 7 Agonists |
| title_fullStr | 3-(5-Hydroxyphenyl)-5-Phenyl-2-Pyrazolines as Toll-Like Receptor 7 Agonists |
| title_full_unstemmed | 3-(5-Hydroxyphenyl)-5-Phenyl-2-Pyrazolines as Toll-Like Receptor 7 Agonists |
| title_short | 3-(5-Hydroxyphenyl)-5-Phenyl-2-Pyrazolines as Toll-Like Receptor 7 Agonists |
| title_sort | 3 5 hydroxyphenyl 5 phenyl 2 pyrazolines as toll like receptor 7 agonists |
| url | http://dx.doi.org/10.1155/2023/2151669 |
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