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解析香豆素类化合物作为单胺氧化酶抑制剂的详细构效关系:最新综述。

Deciphering the detailed structure-activity relationship of coumarins as Monoamine oxidase enzyme inhibitors-An updated review.

机构信息

Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi, India.

Department of Chemistry, Sri Venketeswara College, University of Delhi, New Delhi, India.

出版信息

Chem Biol Drug Des. 2021 Oct;98(4):655-673. doi: 10.1111/cbdd.13919. Epub 2021 Jul 26.

Abstract

In the last few years, Monoamine oxidase (MAO) have emerged as a target for the treatment of many neurodegenerative diseases including anxiety, depression, Alzheimer's, and Parkinson's diseases. The MAO inhibitors especially selective and reversible inhibitors of either of the isoenzymes (MAO-A & MAO-B) have been given more attention as both the form have different therapeutic properties and hence can be used for different neurological disorders. The lack of selective and reversible inhibitors available for both the enzymes and severity of the neuronal disorder in society have opened a new door to the researchers to carry out large and dedicated researches in this field. Among the several classes of the molecule as the inhibitors, coumarins hold a rank as a potent scaffold with its ease of synthesis, high therapeutic potential, and reversibility in inhibiting MAOs. The current review is an update of the research in the field that covers the works during the last six years (2014-2020) with a major focus on the SAR of the coumarin derivatives including synthetic, natural, and hybrids of coumarins with FDA-approved drugs.

摘要

在过去的几年中,单胺氧化酶(MAO)已成为治疗许多神经退行性疾病的靶点,包括焦虑、抑郁、阿尔茨海默病和帕金森病。MAO 抑制剂,特别是单胺氧化酶-A(MAO-A)和单胺氧化酶-B(MAO-B)的选择性和可逆抑制剂,受到了更多关注,因为这两种同工酶具有不同的治疗特性,因此可用于不同的神经紊乱。缺乏针对这两种酶的选择性和可逆抑制剂,以及社会中神经元紊乱的严重性,为研究人员在这一领域开展大型和专门的研究开辟了新的途径。在作为抑制剂的几种分子类别中,香豆素因其易于合成、高治疗潜力和对 MAO 的可逆抑制作用,成为一种有效的支架。本综述是对该领域研究的更新,涵盖了过去六年(2014-2020 年)的工作,主要侧重于香豆素衍生物的 SAR,包括 FDA 批准药物的香豆素的合成、天然和杂合。

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