Kumar Sunil, Nair Aathira Sujathan, Abdelgawad Mohamed A, Mathew Bijo
Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi 682 041, India.
Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka, Al Jouf 72341, Saudi Arabia.
ACS Omega. 2022 May 5;7(19):16244-16259. doi: 10.1021/acsomega.2c01470. eCollection 2022 May 17.
Monoamine oxidase (MAO) is a protein with a key function in the catabolism of neuroamines in both central and peripheral parts of the body. MAO-A and -B are two isozymes of this enzyme which have emerged to be considered as a drug target for the treatment of neurodenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). Isatin is an endogenous small fragment, reversible inhibitor for MAO enzymes and is more selective for MAO-B than -A. Isatin is responsible for increasing the dopamine level in the brain by the inhibition of an MAO enzyme. The very few selective and reversible inhibitors existing for MAO proteins and the intensity of neurological diseases in humanity have opened a new door for researchers. Isatin has a polypharmacological profile in medicinal chemistry, is a reversible inhibitor for both the MAOs, and shows high selectivity potent inhibition for MAO-B. In this review, we discuss isatins and their analogues phthalide and phthalimide with structure-activity relationships (SARs), and this comprehensive information accelerates the ideas for design and development of a new class of MAO inhibitors for neurodegenerative diseases.
单胺氧化酶（MAO）是一种在人体中枢和外周神经胺分解代谢中起关键作用的蛋白质。MAO-A和MAO-B是该酶的两种同工酶，已成为治疗神经退行性疾病如阿尔茨海默病（AD）和帕金森病（PD）的药物靶点。异吲哚酮是一种内源性小片段，是MAO酶的可逆抑制剂，对MAO-B的选择性高于MAO-A。异吲哚酮通过抑制MAO酶来提高大脑中的多巴胺水平。现有的针对MAO蛋白的选择性和可逆抑制剂极少，而人类神经疾病的严重性为研究人员打开了一扇新的大门。异吲哚酮在药物化学中具有多药理学特征，是两种MAO的可逆抑制剂，对MAO-B表现出高选择性强效抑制作用。在这篇综述中，我们讨论异吲哚酮及其类似物苯酞和邻苯二甲酰亚胺的构效关系（SARs），这些全面的信息加速了针对神经退行性疾病的新型MAO抑制剂的设计和开发思路。
