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<p>A series of chromone oxime derivatives containing 1,2,3-triazole moieties were designed, synthesized, and evaluated for their IDO1 inhibitory activities. These compounds displayed moderate to good inhibitory activity against IDO1 with IC<sub>50</sub> values in low micromolar range. Among them, a 7-methoxy-4<i>H</i>-chromone oxime derivative displayed the most potent IDO1 inhibitory activities (hIDO1 IC<sub>50</sub> = 0.084&#xa0;μM, HeLa IDO1 IC<sub>50</sub> = 0.059&#xa0;μM) and was selected for further investigation. Surface plasmon resonance analysis confirmed that the active candidate directly interacted with IDO1 protein with a <i>K</i><sub>D</sub> value of 0.57&#xa0;μM. Molecular docking study revealed the oxygen atom in chromone oxime moiety coordinated to the heme iron, and the 1,2,3-triazole group formed a hydrogen bond with the key residue ARG231. The UV spectra showed that the active candidate induced a Soret peak shift from 404 to 415&#xa0;nm. Furthermore, the active candidate exhibited no cytotoxicity at its effective concentration in MTT assay. In summary, our study suggested that chromone oxime derivatives containing 1,2,3-triazole moieties might serve as a potential agent for the further development of IDO1 inhibitors.</p> Graphical abstract <p></p>

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Design, synthesis, and biological evaluation of novel 1,2,3-triazole chromone oxime derivatives as potent indoleamine 2,3-dioxygenase 1 inhibitors

  • 期刊论文

  • 发表日期：

    2025年8月16日

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  • Zi-Han Fan,
  • Ri-Zhen Huang,
  • Jia-Jia Liu,
  • Mei-Shan Li,
  • Xiao-Teng Jing,
  • Heng-Shan Wang

摘要

A series of chromone oxime derivatives containing 1,2,3-triazole moieties were designed, synthesized, and evaluated for their IDO1 inhibitory activities. These compounds displayed moderate to good inhibitory activity against IDO1 with IC50 values in low micromolar range. Among them, a 7-methoxy-4H-chromone oxime derivative displayed the most potent IDO1 inhibitory activities (hIDO1 IC50 = 0.084 μM, HeLa IDO1 IC50 = 0.059 μM) and was selected for further investigation. Surface plasmon resonance analysis confirmed that the active candidate directly interacted with IDO1 protein with a KD value of 0.57 μM. Molecular docking study revealed the oxygen atom in chromone oxime moiety coordinated to the heme iron, and the 1,2,3-triazole group formed a hydrogen bond with the key residue ARG231. The UV spectra showed that the active candidate induced a Soret peak shift from 404 to 415 nm. Furthermore, the active candidate exhibited no cytotoxicity at its effective concentration in MTT assay. In summary, our study suggested that chromone oxime derivatives containing 1,2,3-triazole moieties might serve as a potential agent for the further development of IDO1 inhibitors.

Graphical abstract