Discovery of Novel 1,2,3-triazole Derivatives as IDO1 Inhibitors

Xixi Hou; Xiaoqing Gong; Longfei Mao; Jie Zhao; Jianxue Yang

doi:10.3390/ph15111316

Discovery of Novel 1,2,3-triazole Derivatives as IDO1 Inhibitors

Pharmaceuticals (Basel). 2022 Oct 25;15(11):1316. doi: 10.3390/ph15111316.

Authors

Xixi Hou¹, Xiaoqing Gong², Longfei Mao^{1

3}, Jie Zhao³, Jianxue Yang^{1

4}

Affiliations

¹ The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China.
² College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China.
³ School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, China.
⁴ School of Nursing, Henan University of Science and Technology, 263 Kaiyuan Road, Luoyang 471003, China.

Abstract

Indoleamine 2,3-dioxygenase 1 (IDO1) has received much attention as an immunomodulatory enzyme in the field of cancer immunotherapy. While several IDO1 inhibitors have entered clinical trials, there are currently no IDO1 inhibitor drugs on the market. To explore potential IDO1 inhibitors, we designed a series of compounds with urea and 1,2,3-triazole structures. Organic synthesis and IDO1 enzymatic activity experiments verified the molecular-level activities of the designed compounds, and the IC₅₀ value of compound 3a was 0.75 μM. Molecular docking and quantum mechanical studies further explained the binding mode and reaction potential of compound 3a with IDO1. Our research has resulted in a series of novel IDO1 inhibitors, which is beneficial to the development of drugs targeting IDO1 in numerous cancer diseases.

Keywords: 1,2,3-triazole; indoleamine 2,3-dioxygenase 1; molecular docking; quantum mechanical studies.

Grants and funding

This study was supported by the Scientific and Technological Project of Henan Province (no. 192102310142).