Effect Produced by a Cyclooctyne Derivative on Both Infarct Area and Left Ventricular Pressure via Calcium Channel Activation.

IF 1.7 Q3 PHARMACOLOGY & PHARMACY

Drug Research Pub Date : 2023-02-01 DOI:10.1055/a-1967-2004

Figueroa-Valverde Lauro, Rosas-Nexticapa Marcela, López-Ramos Maria, Díaz-Cedillo Francisco, Alvarez-Ramirez Magdalena, Mateu-Armad Maria Virginia, Melgarejo-Gutierrez Montserrat

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引用次数: 1

Abstract

Abstract Background There are reports which indicate that some cyclooctyne derivatives may exert changes in cardiovascular system; however, its molecular mechanism is not very clear. Objective The aim of this study was to evaluate the biological activity of four cyclooctyne derivatives (compounds 1 to 4 ) produced on infarct area and left ventricular pressure. Methods Biological activity produced by cyclooctyne derivatives on infarct area was determinate using an ischemia/reperfusion injury model. In addition, to characterize the molecular mechanism of this effect, the following strategies were carried out as follows; i ) biological activity produced by cyclooctyne derivative (compound 4 ) on either perfusion pressure or left ventricular pressure was evaluated using an isolated rat heart; ii ) theoretical interaction of cyclooctyne derivative with calcium channel (1t0j protein surface) using a docking model. Results The results showed that cyclooctyne derivative (compound 4 ) decrease infarct area of in a dose-dependent manner compared with compound 1 to 3 . Besides, this cyclooctyne derivative increase both perfusion pressure and left ventricular pressure which was inhibited by nifedipine. Other theoretical data suggests that cyclooctyne derivative could interact with some aminoacid residues (Met 83 , Ile 85 , Ser 86 , Leu 108 , Glu 114 ) involved in 1t0j protein surface. Conclusions All these data indicate that cyclooctyne derivative increase left ventricular pressure via calcium channel activation and this phenomenon could be translated as a decrease of infarct area.

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环青素衍生物通过激活钙通道对梗死面积和左心室压力的影响。

背景:有报道表明，一些环新生代衍生物可能对心血管系统产生影响;然而，其分子机制尚不清楚。目的:研究四种环青素衍生物(化合物1:~ 4:)对梗死面积和左心室压的影响。方法:采用缺血再灌注损伤模型，测定环新生代衍生物对梗死区域的生物活性。此外，为了表征这种效应的分子机制，我们进行了以下策略:I)利用离体大鼠心脏评价环新因衍生物(化合物4)对灌注压或左心室压产生的生物活性;Ii)基于对接模型的环胱氨酸衍生物与钙通道(1t0j蛋白表面)的理论相互作用。结果:与化合物1∶~ 3∶相比，环青因衍生物(化合物4∶)能显著降低大鼠心肌梗死面积，且呈剂量依赖性。此外，环新因衍生物能增加灌注压和左心室压，而硝苯地平抑制了灌注压和左心室压。其他理论数据表明，环辛基衍生物可以与1t0j蛋白表面的一些氨基酸残基(Met83, Ile85, Ser86, Leu108, Glu114)相互作用。结论:这些数据表明环新素衍生物通过激活钙通道使左室压力升高，这一现象可转化为梗死面积的减少。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug Research PHARMACOLOGY & PHARMACY-

CiteScore

3.50

自引率

0.00%

发文量

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.