合成,抗氧化和神经保护性分析多种功能化的α-aryl-N-alkyl酸盐作为缺血性中风治疗的潜在药物
Alejandro Escobar-Peso1, Emma Martínez-Alonso2, Dimitra Hadjipavlou-Litina3
1Department of Research, Ramón y Cajal University Hospital, IRYCIS, 28034, Madrid, Spain; Laboratory of Medicinal Chemistry, Institute of General Organic Chemistry (CSIC), 28006, Madrid, Spain.
European journal of medicinal chemistry
|January 13, 2024
概括
研究人员合成了新子,以找到用于缺血性中风治疗的神经保护性化合物. 两个化合物 (21a和24a) 在细胞培养和动物模型中都表现出显著的神经保护作用,为中风治疗提供了希望.
科学领域:
- 药用化学 医学化学
- 神经科学是一个神经科学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 缺血性中风仍然是全球死亡和残疾的主要原因.
- 开发有效的神经保护疗法对于改善患者的治疗结果至关重要.
- 阿尔法--N-特特-丁 (PBN) 衍生物因其抗氧化和神经保护潜力而受到探索.
研究的目的:
- 合成和评估一系列32个单替代α-arylnitrones的神经保护作用.
- 为了确定增强神经保护对缺血损伤的结构特征.
- 发现用于治疗缺血性中风的新型治疗剂.
主要方法:
- 基于PBN脚手架的32个α-arylnitron的合成.
- 在缺血条件下使用初级神经元培养物进行神经保护作用的体外评估.
- 在瞬性脑缺血模型中对神经保护和神经缺陷的体内评估.
主要成果:
- 发现N-tert-butyl部分对神经保护活性有益.
- 电子捐赠替代物在形位置和电子吸收替代物在环的元位置与增强活性相关.
- (Z) -N-tert-butyl-1-(2-hydroxyphenyl) methanimine氧化物 (21a) 和 (Z) -N-tert-butyl-1-(2-(prop-2-yn-1-yloxy) phenyl) methanimine氧化物 (24a) 在体外和体内都表现出显著的神经保护作用.
- 化合物21a和24a改善了神经元活力,并减少了神经系统缺陷.
结论:
- 21a和24a是有效的,随时可用的抗氧化剂,具有重要的神经保护性质.
- 这些化合物代表了进一步开发缺血性中风治疗的有希望的候选人.
- 该研究阐明了用于设计强大的神经保护性子的关键结构-活性关系.
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