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有机硒化合物在精神障碍和退行性疾病中的神经药理学。

Neuropharmacology of Organoselenium Compounds in Mental Disorders and Degenerative Diseases.

机构信息

Programa de Pós-Graduação em Biotecnologia (PPGBiotec), Grupo de Pesquisa em Neurobiotecnologia - GPN, CDTec, Universidade Federal de Pelotas, UFPel, Pelotas, RS, Brazil.

Department of Symptom Research, MD Anderson Cancer Center, Houston, United States of America.

出版信息

Curr Med Chem. 2023;30(21):2357-2395. doi: 10.2174/0929867329666220615124412.

Abstract

Neurodegenerative and mental disorders are a public health burden with pharmacological treatments of limited efficacy. Organoselenium compounds are receiving great attention in medicinal chemistry mainly because of their antioxidant and immunomodulatory activities, with a multi-target profile that can favor the treatment of multifactorial diseases. Therefore, the purpose of this review is to discuss recent preclinical studies about organoselenium compounds as therapeutic agents for the management of mental (e.g., depression, anxiety, bipolar disorder, and schizophrenia) and neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis). We have summarized around 70 peer-reviewed articles from 2016 to the present that used in silico, in vitro, and/or in vivo approaches to assess the neuropharmacology of selenium- containing compounds. Among the diversity of organoselenium molecules investigated in the last five years, diaryl diselenides, Ebselen-derivatives, and Se-containing heterocycles are the most representative. Ultimately, this review is expected to provide disease-oriented information regarding the neuropharmacology of organoselenium compounds that can be useful for the design, synthesis, and pharmacological characterization of novel bioactive molecules that can potentially be clinically viable candidates.

摘要

神经退行性和精神障碍是一种公共健康负担,其药物治疗效果有限。有机硒化合物在药物化学中受到极大关注,主要是因为它们具有抗氧化和免疫调节活性,具有多靶点特征,有利于治疗多因素疾病。因此,本综述的目的是讨论最近关于有机硒化合物作为治疗精神(如抑郁症、焦虑症、双相情感障碍和精神分裂症)和神经退行性疾病(如阿尔茨海默病、帕金森病、肌萎缩侧索硬化症和多发性硬化症)的管理的临床前研究。我们总结了大约 70 篇 2016 年至今的同行评议文章,这些文章使用了计算、体外和/或体内方法来评估含硒化合物的神经药理学。在过去五年中研究的各种有机硒分子中,二芳基二硒化物、Ebselen 衍生物和含硒杂环是最具代表性的。最终,本综述有望提供针对有机硒化合物神经药理学的面向疾病的信息,这对于设计、合成和药理学表征新型生物活性分子可能是有用的,这些分子有可能成为有临床应用前景的候选药物。

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