A Novel Competitive Binding Screening Assay Reveals Sennoside B as a Potent Natural Product Inhibitor of TNF-α
Natural products (NPs) have played a significant role in drug discovery for diverse diseases, and numerous attempts have been made to discover promising NP inhibitors of tumor necrosis factor α (TNF-α), a major therapeutic target in autoimmune diseases. However, NP inhibitors of TNF-α, which have th...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-09-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/9/1250 |
| _version_ | 1797520117011054592 |
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| author | Lei Peng Prasannavenkatesh Durai Keunwan Park Jeong Joo Pyo Yongsoo Choi |
| author_facet | Lei Peng Prasannavenkatesh Durai Keunwan Park Jeong Joo Pyo Yongsoo Choi |
| author_sort | Lei Peng |
| collection | DOAJ |
| description | Natural products (NPs) have played a significant role in drug discovery for diverse diseases, and numerous attempts have been made to discover promising NP inhibitors of tumor necrosis factor α (TNF-α), a major therapeutic target in autoimmune diseases. However, NP inhibitors of TNF-α, which have the potential to be developed as new drugs, have not been reported for over a decade. To facilitate the search for new promising inhibitors of TNF-α, we developed an efficient competitive binding screening assay based on analytical size exclusion chromatography coupled with liquid chromatography-tandem mass spectrometry. Application of this screening method to the NP library led to the discovery of a potent inhibitor of TNF-α, sennoside B, with an IC<sub>50</sub> value of 0.32 µM in TNF-α induced HeLa cell toxicity assays. Surprisingly, the potency of sennoside B was 5.7-fold higher than that of the synthetic TNF-α inhibitor SPD304. Molecular docking was performed to determine the binding mode of sennoside B to TNF-α. In conclusion, we successfully developed a novel competition binding screening method to discover small molecule TNF-α inhibitors and identified the natural compound sennoside B as having exceptional potency. |
| first_indexed | 2024-03-10T07:52:17Z |
| format | Article |
| id | doaj.art-6d92d5c3a0d64d8687436d4089a23afc |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T07:52:17Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-6d92d5c3a0d64d8687436d4089a23afc2023-11-22T12:09:16ZengMDPI AGBiomedicines2227-90592021-09-0199125010.3390/biomedicines9091250A Novel Competitive Binding Screening Assay Reveals Sennoside B as a Potent Natural Product Inhibitor of TNF-αLei Peng0Prasannavenkatesh Durai1Keunwan Park2Jeong Joo Pyo3Yongsoo Choi4School of Chemistry and Chemical Engineering, Qiqihar University, Qiqihar 161006, ChinaNatural Product Informatics Research Center, Korea Institute of Science and Technology (KIST), Gangneung 25451, KoreaNatural Product Informatics Research Center, Korea Institute of Science and Technology (KIST), Gangneung 25451, KoreaNatural Product Research Center, Korea Institute of Science and Technology (KIST), Gangneung 25451, KoreaNatural Product Research Center, Korea Institute of Science and Technology (KIST), Gangneung 25451, KoreaNatural products (NPs) have played a significant role in drug discovery for diverse diseases, and numerous attempts have been made to discover promising NP inhibitors of tumor necrosis factor α (TNF-α), a major therapeutic target in autoimmune diseases. However, NP inhibitors of TNF-α, which have the potential to be developed as new drugs, have not been reported for over a decade. To facilitate the search for new promising inhibitors of TNF-α, we developed an efficient competitive binding screening assay based on analytical size exclusion chromatography coupled with liquid chromatography-tandem mass spectrometry. Application of this screening method to the NP library led to the discovery of a potent inhibitor of TNF-α, sennoside B, with an IC<sub>50</sub> value of 0.32 µM in TNF-α induced HeLa cell toxicity assays. Surprisingly, the potency of sennoside B was 5.7-fold higher than that of the synthetic TNF-α inhibitor SPD304. Molecular docking was performed to determine the binding mode of sennoside B to TNF-α. In conclusion, we successfully developed a novel competition binding screening method to discover small molecule TNF-α inhibitors and identified the natural compound sennoside B as having exceptional potency.https://www.mdpi.com/2227-9059/9/9/1250tumor necrosis factor αnatural productssennoside Banalytical size exclusion chromatographyliquid chromatography-tandem mass spectrometry |
| spellingShingle | Lei Peng Prasannavenkatesh Durai Keunwan Park Jeong Joo Pyo Yongsoo Choi A Novel Competitive Binding Screening Assay Reveals Sennoside B as a Potent Natural Product Inhibitor of TNF-α Biomedicines tumor necrosis factor α natural products sennoside B analytical size exclusion chromatography liquid chromatography-tandem mass spectrometry |
| title | A Novel Competitive Binding Screening Assay Reveals Sennoside B as a Potent Natural Product Inhibitor of TNF-α |
| title_full | A Novel Competitive Binding Screening Assay Reveals Sennoside B as a Potent Natural Product Inhibitor of TNF-α |
| title_fullStr | A Novel Competitive Binding Screening Assay Reveals Sennoside B as a Potent Natural Product Inhibitor of TNF-α |
| title_full_unstemmed | A Novel Competitive Binding Screening Assay Reveals Sennoside B as a Potent Natural Product Inhibitor of TNF-α |
| title_short | A Novel Competitive Binding Screening Assay Reveals Sennoside B as a Potent Natural Product Inhibitor of TNF-α |
| title_sort | novel competitive binding screening assay reveals sennoside b as a potent natural product inhibitor of tnf α |
| topic | tumor necrosis factor α natural products sennoside B analytical size exclusion chromatography liquid chromatography-tandem mass spectrometry |
| url | https://www.mdpi.com/2227-9059/9/9/1250 |
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