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取代 1,3,4-噻二唑对心肌梗死病程的免疫调节作用。

Immunomodulatory Action of Substituted 1,3,4-Thiadiazines on the Course of Myocardial Infarction.

机构信息

Institute of Immunology and Physiology of the Ural Branch of RAS, Pervomayskaya 106, Ekaterinburg 620049, Russia.

Department of Pharmacology and Bioinformatics, Volgograd State Medical University, Pavshikh Bortsov Square 1, Volgograd 400131, Russia.

出版信息

Molecules. 2018 Jul 2;23(7):1611. doi: 10.3390/molecules23071611.

Abstract

This review focuses on the biological action of the compounds from the group of substituted 1,3,4-thiadiazines on stress response and myocardial infarction. The aim of this review is to propose the possible mechanisms of action of 1,3,4-thiadiazines and offer prospectives in the development of new derivatives as therapeutic agents. It is known, that compounds that have biological effects similar to those used as antidepressants can down-regulate the secretion of proinflammatory cytokines, up-regulate the release of anti-inflammatory ones and affect cell recruitment, which allows them to be considered immunomodulators as well. The results of pharmacological evaluation, in silico studies, and in vivo experiments of several compounds from the group of substituted 1,3,4-thiadiazines with antidepressant properties are presented. It is proposed that the cardioprotective effects of substituted 1,3,4-thiadiazines might be explained by the peculiarities of their multi-target action: the ability of the compounds to interact with various types of receptors and transporters of dopaminergic, serotonergic and acetylcholinergic systems and to block the kinase signal pathway PI3K-AKT. The described effects of substituted 1,3,4-thiadiazines suggest that it is necessary to search for a new agents for limiting the peripheral inflammatory/ischemic damage through the entral mechanisms of stress reaction and modifying pro-inflammatory cytokine signaling pathways in the brain.

摘要

这篇综述专注于取代 1,3,4-噻二嗪类化合物对应激反应和心肌梗死的生物作用。本文的目的是提出 1,3,4-噻二嗪类化合物可能的作用机制,并为开发新的治疗剂提供新的前景。已知具有与抗抑郁药类似生物效应的化合物可以下调促炎细胞因子的分泌,上调抗炎细胞因子的释放,并影响细胞募集,这使它们也可以被认为是免疫调节剂。本文介绍了几种具有抗抑郁特性的取代 1,3,4-噻二嗪类化合物的药理学评价、计算机模拟研究和体内实验结果。提出取代 1,3,4-噻二嗪类化合物的心脏保护作用可能与其多靶点作用的特点有关:化合物与多巴胺能、血清素能和乙酰胆碱能系统的各种类型受体和转运体相互作用的能力,以及阻断激酶信号通路 PI3K-AKT。取代 1,3,4-噻二嗪类化合物的这些作用表明,有必要通过中枢应激反应机制寻找新的药物来限制外周炎症/缺血性损伤,并改变大脑中促炎细胞因子信号通路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b09/6099947/010b78943255/molecules-23-01611-g001.jpg

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