作为粉样蛋白聚合的有希望的多方面干预剂的埃莫丁衍生物:分子对接/动力学模拟,生物活性评估和细胞保护
Rui Shen1, Wenshuang Zhao1, Xiangyu Li1
1School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, People's Republic of China.
Molecular diversity
|September 22, 2023
概括
埃莫丁衍生物通过多种机制准β-粉样蛋白 (Aβ) 聚合,显示出对抗阿尔茨海默病 (AD) 的承诺. 这些化合物为AD治疗提供了潜在的新疗法策略.
科学领域:
- 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.
- 生物化学 生物化学
背景情况:
- 阿尔茨海默病 (AD) 是一种进展性神经退行性疾病,其特点是β-粉样蛋白 (Aβ) 的错误折叠和积累.
- 通过多方面干预来准Aβ聚合是阿尔茨海默病的一个有希望的治疗策略.
研究的目的:
- 为了研究埃莫丁衍生物 (a-d) 作为阿尔茨海默病的多向定向连接体 (MTDL) 的潜力.
- 评估埃莫丁衍生物在抑制Aβ聚合和防止Aβ诱导的细胞损伤方面的疗效.
主要方法:
- 分子对接和分子动力学模拟用于预测emodin衍生物与Aβ之间的相互作用.
- 在体外测定以评估自我,Cu2+和ACHE诱导的Aβ聚合的抑制.
- 对抗氧化剂活性,神经毒性和细胞保护对氧化和Aβ诱导损伤的评估.
- 用于药理动力学评估的ADMET属性预测.
主要成果:
- 埃莫丁衍生物 (a-d) 显示出强大的多方面干预能力来对抗Aβ聚合.
- 化合物有效地清除过氧基和保护细胞免受氧化和Aβ诱导的损伤,具有最小的神经毒性.
- 预测的ADMET属性表明对emodin衍生物具有合适的药理动力学特征.
结论:
- 埃莫丁衍生物 (a-d) 显示出作为阿尔茨海默病的多向定向联结体 (MTDL) 的巨大潜力.
- 这些发现支持用于AD治疗的天然起源的脚手架修改MTDL的开发.
相关概念视频
Amyloid Fibrils
9.6K
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
9.6K
Alzheimer's Disease: Treatment
212
Alzheimer's Disease (AD), a neurodegenerative disorder, is pathologically identified by amyloid plaques and neurofibrillary tangles composed of tau protein. AD pharmacotherapy aims to manage cognitive symptoms, delay disease progression, and treat behavioral symptoms. The treatment is primarily symptomatic and palliative, with no definitive disease-modifying therapy available. Cholinesterase inhibitors, including donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne), are...
212
Antidepressant Drugs: MAOIs and Other Agents
266
Atypical antidepressants, including bupropion (Wellbutrin), mirtazapine (Remeron), nefazodone (Serzone), trazodone (Desyrel), and vilazodone (Viibryd), offer unique mechanisms of action. Bupropion weakly inhibits dopamine and norepinephrine reuptake, aiding depression treatment and smoking cessation, with a low risk of sexual dysfunction. Mirtazapine enhances serotonin and norepinephrine neurotransmission, leading to sedation, increased appetite, and weight gain. As a result, it helps treat...
266
Adrenergic Agonists: Indirect-Acting Agents
1.7K
Indirect-acting adrenergic agonists potentiate the effects of endogenous catecholamines through different mechanisms without directly binding to adrenoceptors.
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral...
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral...
1.7K
Drugs Affecting Neurotransmitter Synthesis
1.4K
Drugs affecting neurotransmitter synthesis can impact the adrenergic neuron and the synthesis of neurotransmitters. For example, α-methyltyrosine and carbidopa target specific enzymes involved in catecholamine synthesis. α-methyltyrosine inhibits the enzyme tyrosine hydroxylase, which converts tyrosine into dopamine. By blocking this enzyme, α-methyltyrosine reduces dopamine production and other catecholamines. Carbidopa, on the other hand, inhibits the enzyme dopa decarboxylase,...
1.4K


