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作为抗阿尔茨海默病药物的强效多靶点导向配体的探索:基于部分结构的综述

Exploration of Potent Multi-target-directed-ligands as Anti-alzheimer's Disease Agents: A Moiety Based Review.

作者信息

Teli Pankaj, Sahiba Nusrat, Soni Jay, Sethiya Ayushi, Agarwal Dinesh Kumar, Agarwal Shikha

机构信息

Synthetic Organic Chemistry Laboratory, Department of Chemistry, MLSU, Udaipur, India.

Department of Pharmacy, B.N. University, Udaipur, 313001, India.

出版信息

Mini Rev Med Chem. 2021;21(20):3219-3248. doi: 10.2174/1389557521666210304111754.

Abstract

Dementia is a chronic neurodegenerative disease, and a maximum number of the cases are directly related to Alzheimer's disease. More than 4 million people are living with Alzheimer's disease-related dementia in India, making it a national crisis. Alzheimer's disease deteriorates cognitive functions with the passage of time and consists of multi-faceted factors, such as the decline of acetylcholine level, amyloid β-aggregation, tau hyperphosphorylation, oxidative stress, etc. The classical drugs used to date, are focused on only one target and are not serving the cause properly. Hence, the community of scientists is rigorously working on multi-target-directed agents that incorporate two or more active scaffolds in one compound or hybrid of active moieties. This article aims to evaluate novel potential compounds and moieties, such as quinolines, chalcones, coumarins, chromenes, piperazine, carbazoles, cinnamic acids, tacrine hybrids, donepezil hybrids, etc., that have been introduced as multi-target-directed agents in the recent five years.

摘要

痴呆症是一种慢性神经退行性疾病,其中大多数病例与阿尔茨海默病直接相关。在印度,超过400万人患有与阿尔茨海默病相关的痴呆症,这已成为一场全国性危机。随着时间的推移,阿尔茨海默病会使认知功能恶化,它由多方面因素构成,如乙酰胆碱水平下降、淀粉样β蛋白聚集、tau蛋白过度磷酸化、氧化应激等。迄今为止使用的传统药物仅针对一个靶点,无法很好地解决问题。因此,科学家群体正在严格致力于研发多靶点导向药物,即在一种化合物中结合两个或更多活性支架或活性部分的杂合物。本文旨在评估喹啉、查耳酮、香豆素、色烯、哌嗪、咔唑、肉桂酸、他克林杂合物、多奈哌齐杂合物等新型潜在化合物和部分,这些在最近五年中已作为多靶点导向药物被引入。

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