Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by the accumulation of α-synuclein (α-Syn) aggregates. However, there are currently no effective therapies for PD. Brazilin, an inhibitor of α-Syn aggregation, is unstable and toxic. Therefore, we have developed and synthesized derivatives of brazilin. One of these derivatives, called brazilin-7-acetate (B-7-A), has shown reduced toxicity and a stronger effect on inhibiting α-Syn aggregation. It showed that B-7-A prevented the formation of α-Syn fibers and disrupted existing fibers in a dosage-dependent manner. Additionally, B-7-A significantly reduced the cytotoxicity of α-Syn aggregates and alleviated oxidative stress in PC12 cells. The beneficial effects of B-7-A were also confirmed using the Caenorhabditis elegans model. These effects included preventing the accumulation of α-Syn clumps, improving behavior disorder, increasing lifespan, reducing oxidative stress, and protecting against lipid oxidation and loss. Finally, B-7-A showed good ADMET properties in silico. Based on these findings, B-7-A exhibits potential as a prospective treatment for PD.

帕金森病 (PD) 是一种常见的神经退行性疾病，其特征是 α-突触核蛋白 (α-Syn) 聚集体的积累。然而，目前还没有针对PD的有效疗法。 Brazilin 是一种 α-Syn 聚集抑制剂，不稳定且有毒。因此，我们开发并合成了巴西木素的衍生物。其中一种衍生物称为巴西林-7-乙酸酯 (B-7-A)，已显示出较低的毒性和更强的抑制 α-Syn 聚集的作用。结果表明，B-7-A 以剂量依赖性方式阻止 α-Syn 纤维的形成并破坏现有纤维。此外，B-7-A 显着降低了 α-Syn 聚集体的细胞毒性，并减轻了 PC12 细胞的氧化应激。 B-7-A 的有益作用也通过秀丽隐杆线虫模型得到证实。这些作用包括防止 α-Syn 团块的积累、改善行为障碍、延长寿命、减少氧化应激以及防止脂质氧化和损失。最后，B-7-A 在计算机中显示出良好的 ADMET 性能。基于这些发现，B-7-A 显示出作为 PD 前瞻性治疗药物的潜力。