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<p>Compounds containing a 1,3,5-triazine skeleton exhibit broad-spectrum biological activity, particularly in the fields of antiviral, antibacterial, anticancer, and anti-inflammatory properties in medicine. In this study, a series of 1,3,5-triazine derivatives containing morpholine group were designed and synthesized. Their structures were identified by <sup>1</sup>H NMR, <sup>13</sup>C NMR, HRMS and X-ray single crystal diffraction, and their antiviral activity against pseudorabies virus (PRV) and vesicular stomatitis virus (VSV) was evaluated. The results of cell-based assays revealed that some target compounds possessed excellent antiviral effect against PRV and VSV. Compounds <b>10ce</b> (SI: 30.82 against PRV, 16.19 against VSV) and <b>10de</b> (SI: 10.26 against PRV, 13.22 against VSV) exhibited excellent antiviral activity, with significantly higher selectivity indices compared to other derivatives. Further investigations revealed that both compounds effectively inhibited the viral progeny titers of both PRV and VSV. This antiviral activity was corroborated by Western blot and qRT-PCR analyses, which demonstrated significant downregulation of the corresponding viral proteins and their associated genes. Molecular docking studies demonstrated that compounds <b>10ce</b> and <b>10de</b> bound to the active site of PIKfyve with binding energies of -11.2&#xa0;kcal/mol and -11.4&#xa0;kcal/mol, respectively, forming hydrogen bonds and hydrophobic interactions. These findings suggest that their antiviral effects may be mediated through interactions with PIKfyve. Moreover, cytotoxicity assays showed that the CC50 values of compounds <b>10ce</b> and <b>10de</b> were 47.77&#xa0;μM and 46.39&#xa0;μM, respectively, indicating their relatively high safety profiles. These results suggest that 1,3,5-triazine-based compounds are highly promising candidate drugs worthy of further development.</p>

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Synthesis, characterization, and antiviral activity of 1,3,5-triazine derivatives as potential PIKfyve inhibitor

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月31日

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  • Jiayou Xing,
  • Chen Yao,
  • Yingna Xu,
  • Guoyu Yang,
  • Lijun Shi

摘要

Compounds containing a 1,3,5-triazine skeleton exhibit broad-spectrum biological activity, particularly in the fields of antiviral, antibacterial, anticancer, and anti-inflammatory properties in medicine. In this study, a series of 1,3,5-triazine derivatives containing morpholine group were designed and synthesized. Their structures were identified by 1H NMR, 13C NMR, HRMS and X-ray single crystal diffraction, and their antiviral activity against pseudorabies virus (PRV) and vesicular stomatitis virus (VSV) was evaluated. The results of cell-based assays revealed that some target compounds possessed excellent antiviral effect against PRV and VSV. Compounds 10ce (SI: 30.82 against PRV, 16.19 against VSV) and 10de (SI: 10.26 against PRV, 13.22 against VSV) exhibited excellent antiviral activity, with significantly higher selectivity indices compared to other derivatives. Further investigations revealed that both compounds effectively inhibited the viral progeny titers of both PRV and VSV. This antiviral activity was corroborated by Western blot and qRT-PCR analyses, which demonstrated significant downregulation of the corresponding viral proteins and their associated genes. Molecular docking studies demonstrated that compounds 10ce and 10de bound to the active site of PIKfyve with binding energies of -11.2 kcal/mol and -11.4 kcal/mol, respectively, forming hydrogen bonds and hydrophobic interactions. These findings suggest that their antiviral effects may be mediated through interactions with PIKfyve. Moreover, cytotoxicity assays showed that the CC50 values of compounds 10ce and 10de were 47.77 μM and 46.39 μM, respectively, indicating their relatively high safety profiles. These results suggest that 1,3,5-triazine-based compounds are highly promising candidate drugs worthy of further development.