合成和生物评估基于chromanone的衍生物作为潜在的抗神经炎症剂
Guoxun Li1, Xiaoqing Feng1, Wenqian Wang1
1School of Pharmacy, Changzhou University, Changzhou, Jiangsu 213164, China.
Bioorganic chemistry
|August 8, 2023
概括
一种新型的chromanone衍生物,4e通过抑制核因子-kappa B (NF-κB) 激活和促炎性细胞因子产生,有效地减少神经炎症. 这种化合物显示出作为治疗神经炎症相关疾病的神经保护剂的前景.
科学领域:
- 药用化学 医学化学
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
背景情况:
- 克罗曼支架以其多样化的药理学活动而闻名,特别是在管理炎症状况方面.
- 神经炎症在各种神经疾病中起着关键作用,需要开发向治疗剂.
研究的目的:
- 为了合成和评估其抗神经炎症性质的新型chromanone衍生物.
- 在神经炎症的细胞和动物模型中研究最强大的衍生物的作用机制.
主要方法:
- 使用NMR和ESI-HRMS合成和结构性表征克罗曼衍生物.
- 在体外评估氧化 (NO) 释放,可诱导氧化合成酶 (iNOS) 表达和在脂聚糖 (LPS) 诱导的BV-2细胞中的细胞因子产生.
- 在LPS诱导的神经炎症的小鼠模型中体内评估该化合物的疗效,评估微质激活和海马组织反应.
主要成果:
- 克罗曼衍生物4e显示显著抑制NO释放和iNOS表达,没有细胞毒性.
- 化合物4e抑制了核因子-卡帕B (NF-κB) 的转位,并在LPS刺激的BV-2细胞中减少了促炎细胞因子 (TNF-α,IL-6,IL-1β).
- 4e在体内有效地减轻神经炎症,通过抑制LPS治疗小鼠海马中的微质激活,通过TLR4-介导的信号通路禁用NF-κB.
结论:
- 克罗曼衍生物4e通过向NF-κB信号通路,表现出强大的抗神经炎症作用.
- 4e证明了神经保护的潜力,需要进一步研究神经炎症相关疾病的治疗.
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