IHEP OpenIR  > 北京同步辐射装置
Inhibitory investigation of niacin derivatives on metalloenzyme indoleamine 2,3-dioxygenase 1 for its immunomodulatory function
BSRF用户
2021
Source PublicationMETALLOMICS
ISSN1756-5901
EISSN1756-591X
Volume13Issue:3Pages:mfab001
SubtypeArticle
AbstractInhibitors of indoleamine 2,3-dioxygenase 1 (IDO1) have received wide attention for their roles in cancer immunotherapy. It highlights the important role of metalloenzymes in performing human physiological functions. Herein, the recombinant human IDO1 was expressed and purified successfully, and the protein molecule was characterized by SDS-PAGE, MALDI-TOF mass spectrometry, and metalloenzymology. A series of niacin derivatives were investigated with regard to their inhibition on metalloenzyme IDO1, and the resulting potential anti-cancer activities in cell lines. Among the niacin derivatives, 4,4,4-trifluoro-1-(pyridin-3-yl)-butane-1,3-dione (compound 9) was found to be the most effective inhibitor to IDO1 in HepG-2 cells, with an EC50 of 11 mu M with low cytotoxicity. The IC50 value of compound 9 with trifluoroethyl group in enzymatic inhibition was shown to be similar to 5 times more potent than a positive control 4-phenylimidazole. The interaction between compound 9 and IDO1 was verified by isothermal titration calorimetry and molecular docking study. The most favorable molecular docking results revealed that functional groups of compound 9 contributed to the binding of 9 to IDO1 through IDO1-heme coordination, H-bond interactions and hydrophobic contacts. Our finding provides a strategy for the development of new inhibitor candidates for the therapeutic inhibition of IDO1.
DOI10.1093/mtomcs/mfab001
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
WOS IDWOS:000637317500001
ItemNoBSRF00918
beamline1W2B
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ihep.ac.cn/handle/311005/293686
Collection北京同步辐射装置
Recommended Citation
GB/T 7714
BSRF用户. Inhibitory investigation of niacin derivatives on metalloenzyme indoleamine 2,3-dioxygenase 1 for its immunomodulatory function[J]. METALLOMICS,2021,13(3):mfab001.
APA BSRF用户.(2021).Inhibitory investigation of niacin derivatives on metalloenzyme indoleamine 2,3-dioxygenase 1 for its immunomodulatory function.METALLOMICS,13(3),mfab001.
MLA BSRF用户."Inhibitory investigation of niacin derivatives on metalloenzyme indoleamine 2,3-dioxygenase 1 for its immunomodulatory function".METALLOMICS 13.3(2021):mfab001.
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