溶剂和洗剂与胆酶酶的酶动力学研究相容
Dane Sands1, Andrew Davis1, Scott Banfield1
1Department of Medical Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada.
Chemico-biological interactions
|August 14, 2023
概括
某些添加剂可以提高潜在的阿尔茨海默病药物向乙胆化酶 (AChE) 和丁胆化酶 (BChE) 酶的可溶性. 二醇,乙二,甲醇,Tween 20,Tween 80,Brij 35和Brij 96v显示出这些酶的最小抑制.
科学领域:
- 生物化学和酶学 生物化学和酶学
- 药理学 药理学是指药理学的学科.
- 药物发现 药物发现 药物发现
背景情况:
- 乙胆化酶 (AChE) 和丁胆化酶 (BChE) 是关键的酶,参与神经传递和异生物代谢.
- AChE和BChE的抑制剂对于治疗阿尔茨海默病等疾病至关重要.
- 潜在候选药物的低水溶性经常阻碍它们作为胆酶抑制剂的评估.
研究的目的:
- 调查各种辅溶剂和洗剂对胆化酶酶活性的影响.
- 确定增强水溶性的添加剂,而不会显著抑制 AChE 和 BChE.
- 为可溶性较差的候选药物选择合适的溶解剂提供指导.
主要方法:
- 用酶动力学测试来评估潜在的抑制剂.
- 埃尔曼试验被用来测量在不同添加剂的存在下胆酶活性.
- 11种辅助溶剂和6种洗剂对它们对酶功能的影响进行了选.
主要成果:
- 几种辅溶剂和洗剂对胆化酶活性表现出最小的抑制作用.
- 具体来说,发现二醇,乙二,甲醇,多酸盐20 (Tween 20),多酸盐80 (Tween 80),多氧乙烯23烯 (Brij 35) 和多氧乙烯10烯 (Brij 96v) 的抑制作用最小.
- 这些精选的药物有效地促进了水溶性.
结论:
- 辅溶剂和洗剂可以有效地用于克服胆酶抑制剂药物发现中的可溶性挑战.
- 鉴定到的添加剂 (乙烯糖醇,乙二,甲醇,Tween 20,Tween 80,Brij 35,Brij 96v) 是适合用于评估难溶性胆化酶抑制剂的.
- 这项研究通过优化早期药物评估,有助于开发治疗神经系统疾病的新疗法.
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