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Background <p>The current therapeutic options for toxoplasmosis are limited by side effects. The development of molecules against <i>T. gondii</i> is urgently needed. A series of β-carboline derivatives were synthesized and examined as potential agents against toxoplasmosis.</p> Methods <p>A series of β-carboline derivatives were synthesized. To assess their potential as anti-<i>T. gondii</i> agents, cytotoxicity towards Vero cells was determined using the CCK-8 assay. Plaque and qPCR assays were carried out to screen for anti-<i>T. gondii</i> activities, providing insights into their inhibitory effects on the parasite. <i>In vitro</i> assays on <i>T. gondii</i> RH and PRU strains were conducted to evaluate proliferation, invasion, and cyst formation. Transmission electron microscopy was employed to analyze ultrastructural changes and apoptosis in <i>T. gondii</i>, revealing the impact of the derivatives at the cellular level. Finally, the <i>in vivo</i> efficacy of the derivatives was tested in a mouse model, which offered valuable information on their potential therapeutic effects in a living organism.</p> Results <p>β-carboline derivatives exhibited potent inhibitory effects on the growth and replication of both PRU and RH strains, while demonstrating low cytotoxicity to mammalian cells. It is worth noting that NBZ023 and NBZ035 exhibited optimal potency against proliferation (IC<sub>50</sub> = 2.85 and 1.6&#xa0;μM) or invasion (IC<sub>50</sub> = 4.72 and 1.13&#xa0;μM) of <i>T. gondii</i>. Importantly, NBZ023 and NBZ035 had an&#xa0;effect on preventing PRU cysts formation, and they markedly reduced parasite burden in the brain, spleen, and liver in mouse infection model.</p> Conclusions <p>Lead compounds NBZ023 and NBZ035 exhibited an excellent overall efficacy against the <i>T. gondii</i> RH and PRU strains, and were highly effective at preventing toxoplasmosis during murine infection, which are expected to be developed as new anti-toxoplasmosis drugs.</p> Graphical Abstract <p></p>

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Design, synthesis, and anti-Toxoplasma gondii evaluation of β-carboline derivatives

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月29日

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  • Zhendi Liu,
  • Yongmei Li,
  • Yetian Li,
  • Xiaoyu Han,
  • Hongda Qiu,
  • Chang Qin,
  • Yuchao Zhu,
  • Weida Liang,
  • Jiao Mo,
  • Zixun Yan,
  • Weixin Gao,
  • Jiyu Zhang,
  • Jishan Zheng,
  • Hongze Liang,
  • Jili Zhang

摘要

Background

The current therapeutic options for toxoplasmosis are limited by side effects. The development of molecules against T. gondii is urgently needed. A series of β-carboline derivatives were synthesized and examined as potential agents against toxoplasmosis.

Methods

A series of β-carboline derivatives were synthesized. To assess their potential as anti-T. gondii agents, cytotoxicity towards Vero cells was determined using the CCK-8 assay. Plaque and qPCR assays were carried out to screen for anti-T. gondii activities, providing insights into their inhibitory effects on the parasite. In vitro assays on T. gondii RH and PRU strains were conducted to evaluate proliferation, invasion, and cyst formation. Transmission electron microscopy was employed to analyze ultrastructural changes and apoptosis in T. gondii, revealing the impact of the derivatives at the cellular level. Finally, the in vivo efficacy of the derivatives was tested in a mouse model, which offered valuable information on their potential therapeutic effects in a living organism.

Results

β-carboline derivatives exhibited potent inhibitory effects on the growth and replication of both PRU and RH strains, while demonstrating low cytotoxicity to mammalian cells. It is worth noting that NBZ023 and NBZ035 exhibited optimal potency against proliferation (IC50 = 2.85 and 1.6 μM) or invasion (IC50 = 4.72 and 1.13 μM) of T. gondii. Importantly, NBZ023 and NBZ035 had an effect on preventing PRU cysts formation, and they markedly reduced parasite burden in the brain, spleen, and liver in mouse infection model.

Conclusions

Lead compounds NBZ023 and NBZ035 exhibited an excellent overall efficacy against the T. gondii RH and PRU strains, and were highly effective at preventing toxoplasmosis during murine infection, which are expected to be developed as new anti-toxoplasmosis drugs.

Graphical Abstract