合成和神经保护评估的替代印/黄和皮佩里丁杂交物
Qing Zeng1, Ziwei Zhang2, Zhifang Cai1
1National Engineering Research Center for Manufacturing Technology of TCM Solid Preparation, Jiangxi University of Chinese Medicine, Nanchang 330006, China.
ACS chemical neuroscience
|April 24, 2024
概括
新的混合化合物显示出强大的神经保护,防止与中风有关的脑损伤. 化合物4在动物模型中显示出显著的细胞活力和减少了心脏病发作量,这表明它有可能用于治疗神经系统疾病.
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:
- 丁甲基和多尼佩西尔表现出神经保护性.
- 天然甲酸相似物往往具有有限的生物可用性和治疗疗效.
- 开发具有增强神经保护的新型化合物对于治疗神经疾病至关重要.
研究的目的:
- 设计和合成新的英达/黄和皮佩里丁混合物.
- 评估这些化合物的神经保护活性在体外和体内.
- 识别具有改善生物可用性和治疗潜力的化合物.
主要方法:
- 合成英达/黄和皮佩里丁杂交物.
- 在体外评估使用氧气-葡萄糖剥夺/再输液 (OGD/R) 诱导的老鼠初级神经元细胞损伤模型.
- 在体内使用中脑动脉封闭/再输 (MCAO/R) 模型进行体内评估.
- 对血脑屏障的通透性进行并行人工膜通透性测试 (PAMPA).
主要成果:
- 在OGD/R模型中,与1-methylpiperidine结合的印纳衍生物显示出与佐拉类型相比更好的神经保护.
- 十一种化合物 (4,14,15,22,26,35,36,37,48,49和52) 显示出强大的细胞活力和有利的血脑屏障透性.
- 化合物4在MCAO/R模型中显示出显著的神经元细胞活力,没有细胞毒性,并且有效地降低了心脏病发作量 (18.45%在40毫克/公斤).
- 与埃达拉 (20 mg/kg) 相比,化合物4显示出更强的神经保护作用.
结论:
- 合成的英达/黄和皮佩里丁混合物具有显著的神经保护潜力.
- 化合物4是治疗神经系统疾病的有希望的候选者,特别是那些涉及缺血-再输液损伤的人.
- 对化合物4的作用机制和治疗疗效的进一步研究是有必要的.
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