Synthesis and activity study of novel N,N-diphenylurea derivatives as IDO1 inhibitors

Xi-Xi Hou; Zi-Yuan Wu; An Zhan; En Gao; Long-Fei Mao; Hui-Li Wang; Jian-Xue Yang

doi:10.3389/fchem.2023.1222825

Synthesis and activity study of novel N,N-diphenylurea derivatives as IDO1 inhibitors

Front Chem. 2023 Jun 20:11:1222825. doi: 10.3389/fchem.2023.1222825. eCollection 2023.

Authors

Xi-Xi Hou¹, Zi-Yuan Wu^{1

2}, An Zhan^{1

2}, En Gao^{3

4}, Long-Fei Mao⁵, Hui-Li Wang⁶, Jian-Xue Yang^{1

2}

Affiliations

¹ Department of Pharmacy, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China.
² School of Nursing, College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, Luoyang, China.
³ School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, China.
⁴ State Key Laboratory of Quality Research in Chinese Medicine/Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau, China.
⁵ Henan Wanliu Biotechnology Co., Ltd., Luoyang, China.
⁶ UNC Hospital, Chapel Hill, NC, United States.

Abstract

Indoleamine 2,3-dioxygenase 1 (IDO1) has attracted much attention in the field of cancer immunotherapy as an immunomodulatory enzyme. To identify potential IDO1 inhibitors, a novel series of compounds with N,N-diphenylurea and triazole structures were synthesized. The designed compounds underwent organic synthesis, and subsequent enzymatic activity experiments targeting IDO1 confirmed their activity at the molecular level. These experiments provided validation for the efficacy of the designed compounds in inhibiting IDO1, compound 3g exhibited an IC₅₀ value of 1.73 ± 0.97 μM. Further molecular docking study further explained the binding mode and reaction potential of compound 3g 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; N,N-diphenylurea; indoleamine 2,3-dioxygenase 1; inhibitor; molecular docking.