Journal Article

Inhibitory effect of human indoleamine 2,3-dioxygenase 1 (hIDO1) by kazinols of 1,3-diphenylpropane derivatives

Oh, Taehoon, Oh, Seon Min, Park, Mi Hyeon, Jung, Sunin, Lee, Su-Yeon, Ryu, Hyung Won, Kim, Hyoung-Geun, Ko, Sung-Kyun

2024

Overview

This study focused on identifying and characterizing 1,3-diphenylpropane derivatives from flavonoids that inhibit human indoleamine 2,3-dioxygenase 1 (hIDO1) enzymes, which play a role in immune regulation and are associated with various diseases. A series of isolated metabolites (1–7) demonstrated modest to high inhibition of hIDO1, with binding degree values ranging from 26.31 to 72.17%. In particular, during a target-based screening of natural products using hIDO1, kazinol J (6, a 1,3-diphenylpropane derivative) was found to potently inhibit hIDO1, with a binding degree of 72.17% at 1 ppm. Kazinol J (6) showed concentration-dependent and mixed inhibition kinetics and achieved slow and time-dependent inhibition of hIDO1. Additionally, docking simulations were performed to evaluate the inhibitory potential and binding interactions of the compounds with hIDO1. These findings suggest that these 1,3-diphenylpropane derivatives can serve as therapeutic agents for conditions involving hIDO1 dysregulation, such as cancer, autoimmune disorders, and infectious diseases.

• Publisher: Springer Nature B.V
• Subject: Autoimmune diseases / Binding / Biological activity / Cancer / Chemistry / Chromatography / Flavonoids / Immunity (Disease) / Immunoregulation / Infectious diseases / Medical research / Metabolites / Natural products / Pharmacology / Reagents / Research centers / Simulation / Tryptophan 2,3-dioxygenase / Tumors