利用缺血/再灌注损伤模型研究香豆素衍生物对心力衰竭的生物活性

IF 1.7 Q3 PHARMACOLOGY & PHARMACY Drug Research Pub Date : 2024-02-01 Epub Date: 2024-01-17 DOI:10.1055/a-2228-4258
Lauro Figueroa-Valverde, Marcela Rosas-Nexticapa, Magdalena Alvarez-Ramirez, Montserrat Melgarejo-Gutiérrez, Virginia Mateu-Armand, Alejandra Garcimarrero-Espino
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引用次数: 0

摘要

心力衰竭是世界性的健康问题。目前有一些治疗药物,包括地高辛、螺内酯、卡托普利和缬沙坦,但其中一些药物会产生副作用,如心律失常、咳嗽、高钾血症、低钠血症和低血压。本研究的目的是评估香豆素(2H-色烯-2-酮)及其衍生物(3BrAcet-C、3-4Br-Ph-C、4-CN-7D-C、4-Me-7-Ph-C 和 6Br-3-D-C)对缺血再灌注损伤的生物活性,作为心力衰竭的替代治疗药物。此外,还利用离体大鼠心脏模型测定了香豆素衍生物 4-Me-7-Ph-C 在无欧泊班和硝苯地平(剂量为 1 nM)或有欧泊班和硝苯地平存在时对左心室压力(LVP)的生物活性。结果显示:i)与 3BrAcet-C、3-4Br-Ph-C、4-CN-7D-C 和 6Br-3-D-C 相比,香豆素衍生物 4-Me-7-Ph-C 能显著减少梗塞面积(p+=+0.05);ii)4-Me-7-Ph-C 能以剂量依赖的方式增加左心室压,而硝苯地平能抑制这种效应。这些数据表明,香豆素 4-Me-7-Ph-C 可能是一种 L 型钙通道激活剂,因此它可能是一种治疗心力衰竭的良药。
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Biological Activity of a Coumarin Derivative on Heart Failure Using an Ischemia/Reperfusion Injury Model.

Heart failure is a health problem worldwide. There are some drugs for it, including digoxin, spironolactone, captopril, and valsartan, but some of these drugs can produce secondary effects, such as arrhythmia, cough, hyperkalemia, hyponatremia and hypotension. The aim of this research was to evaluate the biological activity of coumarin (2H-chromen-2-one) and its derivatives (3BrAcet-C, 3-4Br-Ph-C, 4-CN-7D-C, 4-Me-7-Ph-C and 6Br-3-D-C) against ischemia/reperfusion injury as a therapeutic alternative for heart failure. In addition, the biological activity of the coumarin derivative 4-Me-7-Ph-C on left ventricular pressure (LVP) was determined in the absence or presence of ouabain and nifedipine at a dose of 1 nM using an isolated rat heart model. The results showed that i) the coumarin derivative 4-Me-7-Ph-C significantly decreased the infarct area (p+=+0.05) compared with 3BrAcet-C, 3-4Br-Ph-C, 4-CN-7D-C, and 6Br-3-D-C; and ii) 4-Me-7-Ph-C increased LVP in a dose-dependent manner, which effect was inhibited by nifedipine. These data suggest that coumarin 4-Me-7-Ph-C may act as a type-L calcium channel activator, so it could be a good agent to treat heart failure.

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来源期刊
Drug Research
Drug Research PHARMACOLOGY & PHARMACY-
CiteScore
3.50
自引率
0.00%
发文量
67
期刊介绍: Drug Research (formerly Arzneimittelforschung) is an international peer-reviewed journal with expedited processing times presenting the very latest research results related to novel and established drug molecules and the evaluation of new drug development. A key focus of the publication is translational medicine and the application of biological discoveries in the development of drugs for use in the clinical environment. Articles and experimental data from across the field of drug research address not only the issue of drug discovery, but also the mathematical and statistical methods for evaluating results from industrial investigations and clinical trials. Publishing twelve times a year, Drug Research includes original research articles as well as reviews, commentaries and short communications in the following areas: analytics applied to clinical trials chemistry and biochemistry clinical and experimental pharmacology drug interactions efficacy testing pharmacodynamics pharmacokinetics teratology toxicology.
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