Discovery of Indoleamine 2,3-Dioxygenase 1 (IDO-1) Inhibitors Based on Ortho-Naphthaquinone-Containing Natural Product
There is great interest in developing small molecules agents capable of reversing tumor immune escape to restore the body’s immune system. As an immunosuppressive enzyme, indoleamine 2,3-dioxygenase 1 (IDO-1) is considered a promising target for oncology immunotherapy. Currently, none of I...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-03-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/24/6/1059 |
| _version_ | 1811316946342248448 |
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| author | Hongchuan Zhao Pu Sun Wei Guo Yi Wang Ao Zhang Linghua Meng Chunyong Ding |
| author_facet | Hongchuan Zhao Pu Sun Wei Guo Yi Wang Ao Zhang Linghua Meng Chunyong Ding |
| author_sort | Hongchuan Zhao |
| collection | DOAJ |
| description | There is great interest in developing small molecules agents capable of reversing tumor immune escape to restore the body’s immune system. As an immunosuppressive enzyme, indoleamine 2,3-dioxygenase 1 (IDO-1) is considered a promising target for oncology immunotherapy. Currently, none of IDO-1 inhibitors have been launched for clinical practice yet. Thus, the discovery of new IDO-1 inhibitors is still in great demand. Herein, a series of diverse ortho-naphthaquinone containing natural product derivatives were synthesized as novel IDO-1 inhibitors. Among them, 1-ene-3-ketone-17-hydroxyl derivative 12 exhibited significantly improved enzymatic and cellular inhibitory activity against IDO-1 when compared to initial lead compounds. Besides, the molecular docking study disclosed that the two most potent compounds 11 and 12 have more interactions within the binding pocket of IDO-1 via hydrogen-bonding, which may account for their higher IDO-1 inhibitory activity. |
| first_indexed | 2024-04-13T11:58:10Z |
| format | Article |
| id | doaj.art-59b9b962d4ec459fac0e1448e0150ed0 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-13T11:58:10Z |
| publishDate | 2019-03-01 |
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| record_format | Article |
| series | Molecules |
| spelling | doaj.art-59b9b962d4ec459fac0e1448e0150ed02022-12-22T02:47:51ZengMDPI AGMolecules1420-30492019-03-01246105910.3390/molecules24061059molecules24061059Discovery of Indoleamine 2,3-Dioxygenase 1 (IDO-1) Inhibitors Based on Ortho-Naphthaquinone-Containing Natural ProductHongchuan Zhao0Pu Sun1Wei Guo2Yi Wang3Ao Zhang4Linghua Meng5Chunyong Ding6CAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, ChinaDivision of Anti-Tumor Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, ChinaDivision of Anti-Tumor Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, ChinaDivision of Anti-Tumor Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, ChinaCAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, ChinaDivision of Anti-Tumor Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, ChinaCAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, ChinaThere is great interest in developing small molecules agents capable of reversing tumor immune escape to restore the body’s immune system. As an immunosuppressive enzyme, indoleamine 2,3-dioxygenase 1 (IDO-1) is considered a promising target for oncology immunotherapy. Currently, none of IDO-1 inhibitors have been launched for clinical practice yet. Thus, the discovery of new IDO-1 inhibitors is still in great demand. Herein, a series of diverse ortho-naphthaquinone containing natural product derivatives were synthesized as novel IDO-1 inhibitors. Among them, 1-ene-3-ketone-17-hydroxyl derivative 12 exhibited significantly improved enzymatic and cellular inhibitory activity against IDO-1 when compared to initial lead compounds. Besides, the molecular docking study disclosed that the two most potent compounds 11 and 12 have more interactions within the binding pocket of IDO-1 via hydrogen-bonding, which may account for their higher IDO-1 inhibitory activity.http://www.mdpi.com/1420-3049/24/6/1059indoleamine 2,3-dioxygenase 1immunosuppressivenatural productortho-naphthaquinonemolecular docking |
| spellingShingle | Hongchuan Zhao Pu Sun Wei Guo Yi Wang Ao Zhang Linghua Meng Chunyong Ding Discovery of Indoleamine 2,3-Dioxygenase 1 (IDO-1) Inhibitors Based on Ortho-Naphthaquinone-Containing Natural Product Molecules indoleamine 2,3-dioxygenase 1 immunosuppressive natural product ortho-naphthaquinone molecular docking |
| title | Discovery of Indoleamine 2,3-Dioxygenase 1 (IDO-1) Inhibitors Based on Ortho-Naphthaquinone-Containing Natural Product |
| title_full | Discovery of Indoleamine 2,3-Dioxygenase 1 (IDO-1) Inhibitors Based on Ortho-Naphthaquinone-Containing Natural Product |
| title_fullStr | Discovery of Indoleamine 2,3-Dioxygenase 1 (IDO-1) Inhibitors Based on Ortho-Naphthaquinone-Containing Natural Product |
| title_full_unstemmed | Discovery of Indoleamine 2,3-Dioxygenase 1 (IDO-1) Inhibitors Based on Ortho-Naphthaquinone-Containing Natural Product |
| title_short | Discovery of Indoleamine 2,3-Dioxygenase 1 (IDO-1) Inhibitors Based on Ortho-Naphthaquinone-Containing Natural Product |
| title_sort | discovery of indoleamine 2 3 dioxygenase 1 ido 1 inhibitors based on ortho naphthaquinone containing natural product |
| topic | indoleamine 2,3-dioxygenase 1 immunosuppressive natural product ortho-naphthaquinone molecular docking |
| url | http://www.mdpi.com/1420-3049/24/6/1059 |
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