与伊萨结合的含有素的乙化衍生物作为具有神经保护作用的单胺氧化酶抑制剂
Sunil Kumar1, Jong Min Oh2, Prabitha Prabhakaran3
1Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi, 682041, India.
Scientific reports
|January 13, 2024
概括
新的以异素为基础的化衍生物显示出对单胺氧化酶 (MAO) 的强烈抑制,特别是MAO-B. 这些化合物表现出神经保护作用,是帕金森病等神经系统疾病的潜在治疗方法.
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:
- 单胺氧化酶 (MAO) 是神经递质代谢中的关键酶.
- 对MAO的失调与各种神经系统疾病有关.
- 基于伊萨的化合物为药物开发提供了一个有前途的支架.
研究的目的:
- 合成和评估用于MAO抑制的基于伊萨丁的新型化衍生物.
- 评估这些化合物的神经保护潜力.
- 阐明化合物与MAO-B的分子相互作用.
主要方法:
- 合成16种以异酸为基础的化衍生物 (IS1-IS16).
- 对于MAO-A和MAO-B的体外酶抑制试验.
- 动力学研究,选择性指数的确定,以及中枢神经系统透性测试 (PAMPA).
- 使用LPS诱导的SH-SY5Y细胞进行体外神经保护试验.
- 分子对接,动态和MM-GBSA用于相互作用分析.
主要成果:
- 所有衍生品都比MAO-A更有效地抑制MAO-B.
- 化合物IS7表现出最强的MAO-B抑制 (IC50 = 0.082μM),而IS15对MAO-A (IC50 = 1.852μM) 是最强的.
- 化合物IS6,IS7和IS13的高选择性指数被观察到与MAO-B.对抗.
- 化合物通过增强抗氧化剂水平和减少炎症标志物来证明中枢神经系统的透性和神经保护作用.
- 分子建模证实了IS7与MAO-B的相互作用.
结论:
- 基于伊萨丁的酸衍生物是具有显著神经保护性质的强有力的MAO抑制剂.
- 化合物,特别是IS7,对像帕金森病这样的神经疾病具有治疗潜力.
- 这项研究为进一步开发这些化合物作为新型治疗剂提供了坚实的基础.
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