奎尔塞丁-1,2,3-三醇混合物作为多功能抗阿尔茨海默氏症剂
Elisabete P Carreiro1, Ana R Costa2,3,4, Célia M Antunes2,3,4
1Institute for Research and Advanced Training (IIFA), LAQV-REQUIMTE, University of Évora, Rua Romão Ramalho 59, 7000-671 Évora, Portugal.
Molecules (Basel, Switzerland)
|November 25, 2023
概括
研究人员开发了新的奎尔塞丁-1,2,3-三醇混合物,作为阿尔茨海默病 (AD) 的潜在治疗方法. 某些杂交物表现出显著的布基胆酶抑制,并对具有低毒性的氧化应激受到保护.
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:
- 阿尔茨海默病 (AD) 是一种进展性神经退行性疾病,患者人数不断增加.
- 目前对阿尔茨海默病的治疗方法有限,需要开发更有效的治疗剂.
- 针对阿兹海默症病理学各个方面的多功能药物非常受欢迎.
研究的目的:
- 为了合成和评估一个库 quercetin-1,2,3-triazole杂交的抗阿尔茨海默病的活动.
- 评估这些新型化合物的抗氧化剂,氧化应激保护和胆酶抑制特性.
- 研究这些杂交物作为AD多功能连接体的潜力.
主要方法:
- 素-1,2,3-二醇混合物 (化合物I-IV) 的合成.
- 在体外评估抗氧化剂和过氧化诱导的氧化应激保护.
- 测定乙胆酶 (AChE) 和丁胆酶 (BuChE) 抑制活性.
- 在试验室中使用Artemia salina测定进行毒性评估.
- 在MCF-7细胞中,细胞活力和对氧化应激的保护作用.
主要成果:
- 杂交物IIf和IVa-d在试验室中强烈抑制了马类丁胆酶 (eqBuChE),其IC50值在11.2至65.7μM之间.
- 混合IIf被确定为最强大的抑制剂,超过了对eqBuChE的IC50为11.2μM的加兰大胺,作为竞争性抑制剂.
- 在Artemia salina测定中观察到有前途的混合体的低毒性;IIf,IVb和IVd对12.5μM的生存能力没有影响.
- 混合物IIf,IVb和IVd在MCF-7细胞中表现出对过氧化诱导的氧化应激产生保护作用.
结论:
- 奎尔赛丁-1,2,3-三混合物代表了阿尔茨海默病 (AD) 治疗中一个有前途的化合物类.
- 混合IIf显示出作为一种针对BuChE抑制和氧化应激的多功能剂的显著潜力.
- 评估的杂交物,特别是IIf,IVb和IVd,充当多功能连接体,解决AD的关键病理.
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