Journal
BIOORGANIC CHEMISTRY
Volume 89, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bioorg.2019.03.044
Keywords
Indoleamine 2,3-dioxygenase 1; Inhibitor; Ubiquinone derivatives; Docking; Halogen bonding
Funding
- State Key Laboratory of Respiratory Disease, China [SKLRD-QN-201709]
- Personalized Medicines - Novel Target-based Antitumor Drug Discovery and Development, Strategic Priority Research Program of the Chinese Academy of Sciences, China [XDA12020336]
- CAS-TWAS
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Indoleamine 2,3-dioxygenase 1 (IDO1) is an attractive therapeutic target for the treatment of cancer, chronic viral infections and neurological disorders characterized by pathological immune stimulation. Herein, a series of known metal-chelating ubiquinone derivatives were designed, synthesized and evaluated for the IDO1 inhibiting activities. The docking studies showed that the compounds 11, 16, 18 and coenzyme-Q1 exhibited different binding modes to IDO1 protein. Among these compounds, the most active compound is 16d with an IC50, of 0.13 mu M in enzymatic assay. The results reveal that a possible halogen bonding interaction between the bromine atom (3-Br) and Cys129 significantly enhances the inhibition activity against IDO1. This study provides structural insights of the interactions between ubiquinone analogues and IDO1 protein for the further modification and optimization.
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