- Site-selective Csp3-H aryloxylation of natural product Tanshinone IIA and its analogues
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A novel catalyst-free Csp3-H aryloxylation approach allowing for rapid installation of a wide range of aryloxyl groups regioselectively at the C-4 position of Tanshinone IIA under simple and mild conditions was developed. This unique protocol exhibited atom-/step-economy, low cost, high efficiency and robust functional-group tolerance, which will greatly facilitate to diversify the A-ring of the bioactive natural product.
- Liang, Bing,Yu, Shujuan,Li, Jie,Wang, Fan,Liang, Gaolin,Zhang, Ao,Ding, Chunyong
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- Discovery of indoleamine 2,3-dioxygenase 1 (IDO-1) inhibitors based on ortho-naphthaquinone-containing natural product
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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.
- Zhao, Hongchuan,Sun, Pu,Guo, Wei,Wang, Yi,Zhang, Ao,Meng, Linghua,Ding, Chunyong
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- Tanshinone IIA derivative with IDO/TDO doubly-selective inhibitory activity
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The invention discloses tanshinone IIA derivatives, or their pharmaceutically acceptable salts, prodrugs, hydrates or solvates, a pharmaceutical composition with the tanshinone IIA derivative acting as an active ingredient, and application of the tanshinone IIA derivative in the preparation of drugs to treat tumors with IDO (indoleamine 2,3-dioxygenase) or TDO (tryptophan 2,3-dioxygenase) overexpression or evidently enhanced activity, such as glioblastoma multiforme, mesothelioma, head and neck cancer, non-small cell lung cancer, bladder cancer and breast cancer, and metabolic disorders, suchobesity, and also provides a preparation method of compounds 1 to 9. Enzymatic activity inhibition experiments prove that the compounds 1-16 can evidently inhibit IDO and TDO, and is suitable for thepreparation of drugs to treat IDO- or ITO-mediated diseases.
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Paragraph 0073-0075
(2019/06/30)
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