AUTHOR=Mao Long-fei , Wang Yu-wei , Zhao Jie , Xu Gui-qing , Yao Xiao-jun , Li Yue-Ming 

TITLE=Discovery of Icotinib-1,2,3-Triazole Derivatives as IDO1 Inhibitors

JOURNAL=Frontiers in Pharmacology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.579024

DOI=10.3389/fphar.2020.579024

ISSN=1663-9812

ABSTRACT=<p>Tumor immunotherapy is considered to be a highlight in cancer treatment in recent years. Indoleamine 2,3-dioxygenase 1 (IDO1) is closely related to the over expression of many cancers, and is therefore a promising target for tumor immunotherapy. To search for novel IDO1-targeting therapeutic agents, 22 icotinib-linked 1,2,3-triazole derivatives were prepared and evaluated for their inhibitory activity against IDO1. The structures of the prepared compounds were confirmed with<sup>1</sup>H NMR, <sup>13</sup>C NMR and HR MS. IDO1 inhibitory activity assay results indicated that 10 of those compounds showed remarkable inhibitory activity against IDO1, among which compound <bold>a17</bold> was the most potent with IC<sub>50</sub>value of 0.37 μM. The binding model between the prepared compounds and IDO1 was studied with molecular modeling study. The current study suggested that icotinib-1,2,3-triazole derivatives could be used as potential inhibitors that preferentially bind to the ferrous form of IDO1 through the formation of coordinate bond with the haem iron.</p>