Identification and preliminary structure-activity relationships of 1-Indanone derivatives as novel indoleamine-2,3-dioxygenase 1 (IDO1) inhibitors

Bioorganic & Medicinal Chemistry
Dingding Gao, Yingxia Li

Abstract

Indoleamine 2,3-dioxygenase 1 (IDO1) plays a vital role in the catabolism of tryptophan along with the kynurenine pathway which is involved in many human diseases including cancer, Alzheimer's disease, etc. In this study, compound 1 bearing a 1-Indanone scaffold was identified as a novel IDO1 inhibitor by structure-based virtual screening, with moderate to good enzymatic and cellular inhibitory activities. Also, surface plasmon resonance analysis validated the direct interaction between compound 1 and IDO1 protein. The preliminary SAR was further explored and the binding mode with IDO1 protein was predicted by experiment along with molecular docking. Subsequent ADME properties of these active compounds were analyzed in silico, and the results showed good pharmacokinetic efficiencies. We believe this study contributes a lot to the structural diversity for the future development of highly potent IDO1 inhibitors.

Citations

Mar 21, 2020·Frontiers in Immunology·Yi-Shu HuangTrevor W Stone
Jan 11, 2020·Computational and Structural Biotechnology Journal·Hee Jin JungHyung Ryong Moon

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