Synthesis and Biological Activity of the Pyridine-hexacyclic-steroid Derivative on a Heart Failure Model.

Q2 Medicine Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry Pub Date : 2022-01-01 DOI:10.2174/1871523021666211222125403

Figueroa-Valverde Lauro, López-Ramos Maria, Díaz-Cedillo Francisco, Rosas-Nexticapa Marcela, Mateu-Armad Maria Virginia, Alvarez-Ramirez Magdalena, Lopez-Gutierrez Tomas, Arakachi-Cruz Idalia

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引用次数: 1

Abstract

Background: Several drugs with inotropic activity have been synthesized; however, there is very little information on biological activity exerted by steroid derivatives in the cardiovascular system.

Objective: The aim of this research was to prepare a steroid-pyridine derivative to evaluate the effect it exerts on left ventricular pressure and characterize its molecular interaction.

Methods: The first stage was carried out through the synthesis of a steroid-pyridine derivative using some chemical strategies. The second stage involved the evaluation of the biological activity of the steroid-pyridine derivative on left ventricular pressure using a model of heart failure in the absence or presence of the drugs, such as flutamide, tamoxifen, prazosin, metoprolol, indomethacin, and nifedipine.

Results: The results showed that steroid-pyridine derivative increased left ventricular pressure in a dose-dependent manner (0.001-100 nM); however, this phenomenon was significantly inhibited only by nifedipine at a dose of 1 nM. These results indicate that positive inotropic activity produced by the steroid-pyridine derivative was via calcium channel activation. Furthermore, the biological activity exerted by the steroid-pyridine derivative on the left ventricle produces changes in cAMP concentration.

Conclusion: It is noteworthy that positive inotropic activity produced by this steroid-pyridine derivative involves a different molecular mechanism compared to other positive inotropic drugs. Therefore, this steroid could be a good candidate for the treatment of heart failure.

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吡啶-六环类固醇衍生物在心力衰竭模型上的合成及生物活性。

背景:已经合成了几种具有肌力活性的药物;然而，关于类固醇衍生物在心血管系统中发挥的生物活性的信息很少。目的:制备甾体吡啶衍生物，研究其对左心室压力的影响，并表征其分子相互作用。方法:第一阶段采用一定的化学策略合成甾体吡啶衍生物。第二阶段包括评估类固醇吡啶衍生物在氟他胺、他莫昔芬、吡唑嗪、美托洛尔、吲哚美辛和硝苯地平等药物缺席或存在时对左心室压力的生物活性。结果:甾体吡啶衍生物使左室压呈剂量依赖性升高(0.001 ~ 100 nM);然而，只有1 nM剂量的硝苯地平才能显著抑制这种现象。这些结果表明类固醇吡啶衍生物通过激活钙通道产生正性肌力活性。此外，类固醇吡啶衍生物对左心室的生物活性产生cAMP浓度的变化。结论:值得注意的是，与其他正性肌力药物相比，这种类固醇吡啶衍生物产生正性肌力活性的分子机制不同。因此，这种类固醇可能是治疗心力衰竭的一个很好的候选者。

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

Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry Pharmacology, Toxicology and Pharmaceutics-Pharmacology

CiteScore

3.30

自引率

0.00%

发文量

期刊介绍： Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of new anti-inflammatory & anti-allergy agents. Publishing a series of timely in-depth reviews written by leaders in the field covering a range of current topics, Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in the field.