Inhibitory effects of flavonoids isolated from Sophora flavescens on indoleamine 2,3-dioxygenase 1 activity

Journal of Enzyme Inhibition and Medicinal Chemistry

In-Ja Ryoo¹  Sangkeun Son¹  Gun-Hee Kim¹  Bo Yeon Kim²  Jong Seog Ahn²  Mina Jang²  Mincheol Kwon²  Jae-Hyuk Jang³  Sei-Ryang Oh⁴  Sung-Kyun Ko⁴  Hyung Won Ryu⁴  Won-Kyu Lee⁵ 

[1] Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, Korea;Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, Korea;Department of Biomolecular Science, KRIBB School of Bioscience, Korea University of Science and Technology, Daejeon, Korea;Department of Biomolecular Science, KRIBB School of Bioscience, Korea University of Science and Technology, Daejeon, Korea;Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, Korea;Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, Korea;New Drug Development Center, Osong Medical Innovation Foundation, Cheongju, Kore;

关键词: Indoleamine 2,3-dioxygenase 1 (IDO1);    IDO1 inhibitor;    Sophora flavescens;    flavonoid;   

DOI  :  10.1080/14756366.2019.1640218

来源: publisher

【 摘 要 】

Indoleamine 2,3-dioxygenase 1 (IDO1), a tryptophan catabolising enzyme, is known as a tumour cell survival factor that causes immune escape in several types of cancer. Flavonoids of Sophora flavescens have a variety of biological benefits for humans; however, cancer immunotherapy effect has not been fully investigated. The flavonoids (1–6) isolated from S. flavescens showed IDO1 inhibitory activities (IC50 4.3–31.4 µM). The representative flavonoids (4–6) of S. flavescens were determined to be non-competitive inhibitors of IDO1 by kinetic analyses. Their binding affinity to IDO1 was confirmed using thermal stability and surface plasmon resonance (SPR) assays. The molecular docking analysis and mutagenesis assay revealed the structural details of the interactions between the flavonoids (1–6) and IDO1. These results suggest that the flavonoids (1–6) of S. flavescens, especially kushenol E (6), as IDO1 inhibitors might be useful in the development of immunotherapeutic agents against cancers.

【 授权许可】

CC BY