植物多基黄如何阻碍细胞染色体3A4的新陈代谢?
Carina S P Vieira1, Marisa Freitas1, Andreia Palmeira2,3
1Associated Laboratory for Green Chemistry (LAQV), Network of Chemistry and Technology (REQUIMTE), Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.
Biomedicines
|March 28, 2025
概括
像贝卡莱因和斯库特拉林这样的黄类化合物强烈抑制细胞染色体P450 3A4 (CYP3A4) 酶活性. 它们的基团是与酶结合的关键.
科学领域:
- 药理学 药理学是指药理学的学科.
- 生物化学 生物化学
- 药物新陈代谢 药物新陈代谢
背景情况:
- 饮食成分可以通过影响异生菌代谢来调节药物药理动力学.
- 细胞染色体P450 3A4 (CYP3A4) 是一个关键的酶在代谢超过一半的所有异生菌.
- 在食物和补充剂中发现的黄类化合物具有不同的生物活动,受其化学结构的影响.
研究的目的:
- 调查各种多基黄类药物对CYP3A4活性的抑制潜力.
- 通过分子对接,阐明强大的黄类抑制剂和CYP3A4活性位点之间的相互作用机制.
主要方法:
- 高通量度测定以选15种多基黄类物质对CYP3A4的抑制.
- 首次评估皮蛋白和皮蛋白的抑制作用.
- 对顶级抑制剂与CYP3A4酶活性部位的分子对接分析.
主要成果:
- 拜卡莱因 (IC50: 15 ± 5 μmol/L),斯库特拉莱因 (IC50: 19 ± 7 μmol/L) 和黄素是最强效的黄素.
- 戈西佩丁 (IC50: 40 ± 8 μmol/L),赫巴塞丁 (IC50: 32 ± 8 μmol/L) 和奎尔塞丁是最强效的黄醇.
- 对接显示,特定位置 (C6,C7,C8,C3') 的基组对于与CYP3A4基质结合部位的结合至关重要.
结论:
- 拜卡莱因和斯库特拉莱因表现出强烈的CYP3A4抑制,与已知的抗病毒和抗真菌药物相当.
- 黄类化合物的邻基对于它们在CYP3A4催化部位内的强度结合和稳定至关重要.
相关概念视频
01:17Drug Metabolism: Phase I Reactions
5.8K
A phase I reaction is a biochemical process that introduces a functionally reactive polar group to a substance. This transformation predominantly occurs in the liver, facilitated by the cytochrome P450 system of hemoproteins situated in the lipophilic endoplasmic reticulum of cells. The metabolite generated through this process can have varying polarities. If it is sufficiently polar, it can be easily excreted in the urine due to its water compatibility. However, if the metabolite is nonpolar,...
5.8K
01:25Pharmacokinetics: Drug–Drug Interactions
743
Drug interactions occur when the pharmacological effect of one drug is altered by another substance, either enhancing or diminishing its activity. The drug whose activity is altered is known as the object drug, and the substance causing the alteration is called the agent drug or the precipitant. The net effects of these interactions are mostly undesirable, leading to decreased effectiveness or increased adverse effects. In rare cases, interactions can be beneficial, such as the enhanced...
743
01:26Pharmacokinetics: Drug–Food and Drug–Viral Interactions
618
A drug interaction occurs when the concurrent use of another drug, food, or an external substance alters the pharmacological activity of a drug. This interaction can modify the action of the original drug, affecting its effectiveness and safety.Drug–food interactions are significant as they impact drug absorption, metabolism, and excretion. For example, grapefruit juice is a well-known disruptor of drug metabolism. It inhibits the cytochrome P450 3A4 enzyme, crucial for the metabolism of...
618
01:18Pharmacokinetics in Geriatric Patients: Effect of Age on Drug Metabolism
354
Geriatric patients show significant variation in how their bodies process medications, which can change how effective and safe treatments are. The liver is the primary organ where drug metabolism occurs, involving two main types of chemical reactions: phase I and II. Phase I metabolism is driven by the cytochrome P450 enzyme system, which includes key types such as CYP3A, CYP2D6, and CYP2C9. Research indicates that while aging doesn't notably alter the levels or activity of these enzymes, it...
354
01:27Pharmacogenetics of Drug Metabolism: Overview
150
Genetic polymorphism in drug metabolism is crucial to the inter-individual variability observed in drug responses. Drug metabolism primarily involves the chemical modification of drugs and other xenobiotics to enhance their elimination by increasing their polarity. Two main classes of enzymes mediate this biotransformation process: Phase I enzymes, primarily cytochrome P450s, catalyze oxidation and reduction reactions, while other enzymes, such as esterases, mediate hydrolysis, and Phase II...
150
01:28Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes
228
Cytochrome P450 (CYP450) enzymes are a superfamily of heme-containing monooxygenases that play a pivotal role in Phase I drug metabolism by catalyzing oxidation and reduction reactions.These enzymes transform lipophilic xenobiotics into more hydrophilic metabolites, facilitating subsequent Phase II conjugation and eventual excretion. The CYP450 family is classified into families (e.g., CYP1–CYP3) and subfamilies (e.g., CYP2A, CYP2C), based on amino acid sequence homology.CYP450...
228