新型跨咖啡酸衍生物:合成,抑制氧化 (NO) 生产和分子对接研究
Trinh Thi Thuy1,2, Nguyen Thi Thuy Linh1,2, Hoa Nguyen Thi Thu1,3,4
1Graduate University of Science and Technology, Vietnam Academy of Science and Technology, Cau Giay, Hanoi, Vietnam.
Natural product research
|October 20, 2023
概括
合成了新的咖啡化衍生物,并测试了它们的抗炎活性. 化合物4f,4g和4h显示出巨细胞中氧化产生的强烈抑制.
科学领域:
- 药用化学 医学化学
- 药理学 药理学是指药理学的学科.
- 有机合成 有机合成
背景情况:
- 炎症是一种复杂的生物反应,与各种疾病有关.
- 氧化 (NO) 在炎症过程中起着至关重要的作用.
- 开发新的抗炎药物是一个重要的治疗目标.
研究的目的:
- 为了合成新的咖啡化衍生物.
- 通过抑制氧化生产来评估这些衍生物的抗炎潜力.
- 通过分子对接研究来研究作用机制.
主要方法:
- 通过化合成八种咖啡化衍生物 (4a-4h).
- 在RAW264.7巨中对脂聚糖 (LPS) 诱导的氧化 (NO) 生产的抑制作用的体外评估.
- 对诱导性氧化合成酶 (iNOS) 的分子对接研究.
主要成果:
- 化合物4f,4g和4h表现出强烈的抗炎活性,IC50值在11.90至24.17μM之间,优于参考L-NMMA.
- 分子对接揭示了化合物4f,4h,4a和4g与iNOS受体的有效结合,对接分数低至-11.62 kcal/mol.
- 合成的衍生物显示出作为炎症途径抑制剂的有前途潜力.
结论:
- 新型咖啡化衍生物具有显著的抗炎性质.
- 化合物4f,4g和4h被确定为进一步开发抗炎药物的主要候选物.
- 分子对接提供了对iNOS的抑制机制的见解.
相关概念视频
Aldehydes and Ketones with HCN: Cyanohydrin Formation Overview
2.8K
Cyanohydrins are compounds that contain –CN and –OH groups on the same carbon atom. They are formed by the nucleophilic addition of the cyanide ions to the carbonyl group. Cyanide ions are highly basic and nucleophilic and can be generated from HCN under aqueous conditions. However, since HCN is a weak acid, the number of cyanide ions generated is very small. Hence, a small amount of base or KCN/NaCN is added to HCN to increase the concentration of the cyanide ions in the reaction...
2.8K
Aldehydes and Ketones with HCN: Cyanohydrin Formation Mechanism
3.2K
Cyanohydrins are formed when cyanide nucleophiles and carbonyl compounds like aldehydes and ketones react. A strong base, the cyanide ion, catalyzes cyanohydrin formation. The ions are generated from HCN under aqueous conditions. Once the cyanide ions are generated, the first step involves the nucleophilic attack of the cyanide ions on the electrophilic carbonyl carbon. This attack shifts the π electrons from the C=O to the oxygen atom forming the alkoxide ion intermediate. The alkoxide anion...
3.2K
Diazonium Group Substitution: –OH and –H
2.8K
Nitrous acid, a weak acid, is prepared in situ via the reaction of sodium nitrite with a strong acid under cold conditions. This nitrous acid prepared in situ reacts with primary arylamines to form arenediazonium salts. Such reactions are known as diazotization reactions. As shown in Figure 1, the formation of arenediazonium salts begins with the decomposition of nitrous acid in an acidic solution to give nitrosonium ions.
2.8K
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
Adrenergic Agonists: Indirect-Acting Agents
1.6K
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...
1.6K
Antihypertensive Drugs: Vasodilators
543
Vasodilators, primarily affecting the smooth muscles within arterial and venous walls, are commonly used for hypertension treatment. Medications such as minoxidil and hydralazine primarily target arteries and arterioles, while sodium nitroprusside acts on arterioles and venules. Minoxidil, functioning as a prodrug, is metabolized by hepatic sulfotransferase into its active form, minoxidil sulfate, after oral administration. This metabolite binds to the sulfonylurea receptor (SUR) component of...
543


