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Discovery of Indoleamine 2,3-Dioxygenase 1 (IDO-1) Inhibitors Based on Ortho -Naphthaquinone-Containing Natural Product.

Research paper by Hongchuan H Zhao, Pu P Sun, Wei W Guo, Yi Y Wang, Ao A Zhang, Linghua L Meng, Chunyong C Ding

Indexed on: 22 Mar '19Published on: 21 Mar '19Published in: Molecules (Basel, Switzerland)



Abstract

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 -naphthaquinone containing natural product derivatives were synthesized as novel IDO-1 inhibitors. Among them, 1-ene-3-ketone-17-hydroxyl derivative 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 and have more interactions within the binding pocket of IDO-1 via hydrogen-bonding, which may account for their higher IDO-1 inhibitory activity.