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

Abstract

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 (IC 50 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.

Determination of Alkaloids and Flavonoids in Sophora flavescens by UHPLC-Q-TOF/MS

“…Indoleamine 2-dioxygenase-1 (IDO1), a tumor cell survival factor, can lead to the escape of many kinds of cancer cells. As inhibitors of IDO1, many flavonoids in Sophora flavescens have potential uses in cancer immunotherapy [ 9 ]. In view of the good clinical efficacy and research prospects of Sophora flavescens , it is of great significance to establish a technique that can quickly classify and identify the chemical composition of Sophora flavescens .…”

Jejucarbazoles A–C, carbazole glycosides with indoleamine 2,3-dioxygenase 1 inhibitory activity fromStreptomycessp. KCB15JA151

“…A literature study revealed several modes of IDO1 inhibition 18,31 through an allosteric regulator, 38 heme-binder, 23 and heme-displacer. 16 Qinglin Pu et al compared the activities of the IDO1 inhibitors in clinical trials, which showed that the inhibition by the heme-displacing mode is more potent due to its larger interaction interface with IDO1 enzyme by reason of the absence of the bulky heme moiety.…”

Kurarinone Attenuates BLM-Induced Pulmonary Fibrosis via Inhibiting TGF-β Signaling Pathways

“…Flavonoids including kurarinone (Figure S1A) were isolated from S. flavescens and purified using the method described by Kwon et al and Lee et al [24,25]. Purity was measured at 97.46% by ultra-performance liquid chromatography (UPLC) (Figure S1B).…”