Novel β-Cyclodextrin-Based Heptavalent Glycyrrhetinic Acid Conjugates: Synthesis, Characterization, and Anti-Influenza Activity
In our continuing efforts toward the design of novel pentacyclic triterpene derivatives as potential anti-influenza virus entry inhibitors, a series of homogeneous heptavalent glycyrrhetinic acid derivatives based on β-cyclodextrin scaffold were designed and synthesized by click chemistry. The struc...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2022.836955/full |
| _version_ | 1819046125529726976 |
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| author | Shuobin Liang Xinyuan Ma Man Li Yanliang Yi Qianqian Gao Yongmin Zhang Lihe Zhang Demin Zhou Demin Zhou Demin Zhou Sulong Xiao |
| author_facet | Shuobin Liang Xinyuan Ma Man Li Yanliang Yi Qianqian Gao Yongmin Zhang Lihe Zhang Demin Zhou Demin Zhou Demin Zhou Sulong Xiao |
| author_sort | Shuobin Liang |
| collection | DOAJ |
| description | In our continuing efforts toward the design of novel pentacyclic triterpene derivatives as potential anti-influenza virus entry inhibitors, a series of homogeneous heptavalent glycyrrhetinic acid derivatives based on β-cyclodextrin scaffold were designed and synthesized by click chemistry. The structure was unambiguously characterized by NMR, IR, and MALDI-TOF-MS measurements. Seven conjugates showed sufficient inhibitory activity against influenza virus infection based on the cytopathic effect reduction assay with IC50 values in the micromolar range. The interactions of conjugate 37, the most potent compound (IC50 = 2.86 μM, CC50 > 100 μM), with the influenza virus were investigated using the hemagglutination inhibition assay. Moreover, the surface plasmon resonance assay further confirmed that compound 37 bound to the influenza HA protein specifically with a dissociation constant of 5.15 × 10−7 M. Our results suggest the promising role of β-cyclodextrin as a scaffold for preparing a variety of multivalent compounds as influenza entry inhibitors. |
| first_indexed | 2024-12-21T10:39:30Z |
| format | Article |
| id | doaj.art-63e56b202e9a40899d763e8c4dde9679 |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-12-21T10:39:30Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-63e56b202e9a40899d763e8c4dde96792022-12-21T19:06:57ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462022-04-011010.3389/fchem.2022.836955836955Novel β-Cyclodextrin-Based Heptavalent Glycyrrhetinic Acid Conjugates: Synthesis, Characterization, and Anti-Influenza ActivityShuobin Liang0Xinyuan Ma1Man Li2Yanliang Yi3Qianqian Gao4Yongmin Zhang5Lihe Zhang6Demin Zhou7Demin Zhou8Demin Zhou9Sulong Xiao10State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, ChinaSorbonne Université, Institut Parisien de Chimie Moléculaire, CNRS UMR 8232, Paris, FranceState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, ChinaInstitute of Chemical Biology, Shenzhen Bay Laboratory, Shenzhen, ChinaNingbo Institute of Marine Medicine, Peking University, Ningbo, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, ChinaIn our continuing efforts toward the design of novel pentacyclic triterpene derivatives as potential anti-influenza virus entry inhibitors, a series of homogeneous heptavalent glycyrrhetinic acid derivatives based on β-cyclodextrin scaffold were designed and synthesized by click chemistry. The structure was unambiguously characterized by NMR, IR, and MALDI-TOF-MS measurements. Seven conjugates showed sufficient inhibitory activity against influenza virus infection based on the cytopathic effect reduction assay with IC50 values in the micromolar range. The interactions of conjugate 37, the most potent compound (IC50 = 2.86 μM, CC50 > 100 μM), with the influenza virus were investigated using the hemagglutination inhibition assay. Moreover, the surface plasmon resonance assay further confirmed that compound 37 bound to the influenza HA protein specifically with a dissociation constant of 5.15 × 10−7 M. Our results suggest the promising role of β-cyclodextrin as a scaffold for preparing a variety of multivalent compounds as influenza entry inhibitors.https://www.frontiersin.org/articles/10.3389/fchem.2022.836955/fullglycyrrhetinic acidβ-cyclodextrininfluenza virusmultivalencyhemagglutinin |
| spellingShingle | Shuobin Liang Xinyuan Ma Man Li Yanliang Yi Qianqian Gao Yongmin Zhang Lihe Zhang Demin Zhou Demin Zhou Demin Zhou Sulong Xiao Novel β-Cyclodextrin-Based Heptavalent Glycyrrhetinic Acid Conjugates: Synthesis, Characterization, and Anti-Influenza Activity Frontiers in Chemistry glycyrrhetinic acid β-cyclodextrin influenza virus multivalency hemagglutinin |
| title | Novel β-Cyclodextrin-Based Heptavalent Glycyrrhetinic Acid Conjugates: Synthesis, Characterization, and Anti-Influenza Activity |
| title_full | Novel β-Cyclodextrin-Based Heptavalent Glycyrrhetinic Acid Conjugates: Synthesis, Characterization, and Anti-Influenza Activity |
| title_fullStr | Novel β-Cyclodextrin-Based Heptavalent Glycyrrhetinic Acid Conjugates: Synthesis, Characterization, and Anti-Influenza Activity |
| title_full_unstemmed | Novel β-Cyclodextrin-Based Heptavalent Glycyrrhetinic Acid Conjugates: Synthesis, Characterization, and Anti-Influenza Activity |
| title_short | Novel β-Cyclodextrin-Based Heptavalent Glycyrrhetinic Acid Conjugates: Synthesis, Characterization, and Anti-Influenza Activity |
| title_sort | novel β cyclodextrin based heptavalent glycyrrhetinic acid conjugates synthesis characterization and anti influenza activity |
| topic | glycyrrhetinic acid β-cyclodextrin influenza virus multivalency hemagglutinin |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2022.836955/full |
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