基于丁三醇的双胆酶抑制剂的光化学辅助合成
Antonija Jelčić1, Stanislava Talić2, Ilijana Odak2
1Department of Organic Chemistry, University of Zagreb Faculty of Chemical Engineering and Technology, Trg Marka Marulića 19, HR-10 000 Zagreb, Croatia.
新型充电的丁-1,2,3-盐显示出对乙胆酶 (AChE) 和丁胆酶 (BChE) 的强烈抑制. 这些化合物,特别是1,2和8,在阿尔茨海默病治疗中具有治疗潜力.
科学领域:
- 医学化学
- 神经科学
- 有机合成
背景情况:
- 诺-1,2,3-醇是已知选择性抑制剂的丁胆酶 (BChE).
- 充电衍生物 (盐) 也抑制了乙胆酶 (AChE),这是阿尔茨海默病治疗中至关重要的酶.
- 与中性类型相比,盐具有较强的BCH抑制.
研究的目的:
- 合成和生物评估新型充电的丁-1,2,3-盐 (化合物1-17).
- 研究它们作为阿尔茨海默病治疗的双重抑制剂.
主要方法:
- 硫-1,2,3-骨架的光化学合成
- 转换为相应的化盐.
- 使用核磁共振 (NMR) 和高分辨率质谱 (HRMS) 进行结构确认.
- 在体外酶抑制测定 AChE 和 BChE.
主要成果:
- 所有合成的化合物都表现出中度至强度的BCH抑制和中度的ACH抑制.
- 化合物8和11是强大的ACH抑制剂 (IC50~2. 6- 3. 2μM).
- 化合物1,2和8显示出优异的选择性BCH抑制 (IC50~0. 3~0. 4μM),表现优于胺.
- 化合物17具有有限的抗炎活性,降低了TNF-α的产生.
结论:
- 电荷和替代剂类型显著调节生物活动.
- 合成的分子作为双胆酶抑制剂具有治疗潜力.
- 对于治疗像阿尔茨海默氏症这样的神经退行性疾病, 需要进一步发展.
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