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

• Published in: Molecules (Basel, Switzerland) Vol. 23; no. 7; p. 1611
• Main Authors: Sarapultsev, Alexey P, Vassiliev, Pavel M, Sarapultsev, Petr A, Chupakhin, Oleg N, Ianalieva, Laura R, Sidorova, Larisa P
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 02.07.2018; MDPI
• Subjects: 1,3,4-thiadiazines; 1-Phosphatidylinositol 3-kinase; AKT protein; Animals; Antidepressants; Biological effects; Cellular stress response; Chemical compounds; Cytokines; Cytokines - metabolism; Dopamine receptors; Heart attacks; Humans; Immunologic Factors - pharmacology; Immunologic Factors - therapeutic use; Immunomodulation; Immunomodulators; In vivo methods and tests; Inflammation; Inflammation - drug therapy; Inflammation - metabolism; Ischemia; Myocardial infarction; Myocardial Infarction - drug therapy; Pharmacology; Phosphatidylinositol 3-Kinases - metabolism; PI3K-AKT signaling pathway; Review; Serotonin transporter; Signal Transduction - drug effects; stress response; Substitutes; Thiadiazines - pharmacology; Thiadiazines - therapeutic use; immunomodulators; 1,3,4-thiadiazines; stress response; PI3K-AKT signaling pathway; myocardial infarction
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules23071611

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.