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新型多靶点药物设计：以多奈哌齐为基础的杂合及天然产物在阿尔茨海默病治疗中的应用

New Insights into the Development of Donepezil-Based Hybrid and Natural Molecules as Multi-Target Drug Agents for Alzheimer's Disease Treatment.

机构信息

Department of Chemistry, Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria.

Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria.

出版信息

Molecules. 2024 Nov 11;29(22):5314. doi: 10.3390/molecules29225314.

DOI:10.3390/molecules29225314
PMID:39598703
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11596391/
Abstract

Alzheimer's disease (AD) involves a complex pathophysiology with multiple interconnected subpathologies, including protein aggregation, impaired neurotransmission, oxidative stress, and microglia-mediated neuroinflammation. Current treatments, which generally target a single subpathology, have failed to modify the disease's progression, providing only temporary symptom relief. Multi-target drugs (MTDs) address several subpathologies, including impaired aggregation of pathological proteins. In this review, we cover hybrid molecules published between 2014 and 2024. We offer an overview of the strategies employed in drug design and approaches that have led to notable improvements and reduced hepatotoxicity. Our aim is to offer insights into the potential development of new Alzheimer's disease drugs. This overview highlights the potential of multi-target drugs featuring heterocycles with -benzylpiperidine fragments and natural compounds in improving Alzheimer's disease treatment.

摘要

阿尔茨海默病（AD）涉及一个复杂的病理生理学，包括多种相互关联的亚病理生理学，包括蛋白质聚集、神经传递受损、氧化应激和小胶质细胞介导的神经炎症。目前的治疗方法通常针对单一的亚病理生理学，未能改变疾病的进展，只能提供暂时的症状缓解。多靶点药物（MTDs）针对多种亚病理生理学，包括病理性蛋白聚集的受损。在这篇综述中，我们涵盖了 2014 年至 2024 年期间发表的混合分子。我们提供了药物设计中使用的策略和方法的概述，这些策略和方法导致了显著的改善和降低了肝毒性。我们的目的是为新的阿尔茨海默病药物的开发提供见解。这篇综述强调了具有 -苄基哌啶片段和天然化合物的杂环的多靶点药物在改善阿尔茨海默病治疗方面的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efe5/11596391/3cd47d8c921d/molecules-29-05314-g013.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efe5/11596391/1918ea6242ca/molecules-29-05314-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efe5/11596391/b9bbbbc7f0ab/molecules-29-05314-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efe5/11596391/d53725669009/molecules-29-05314-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efe5/11596391/e07f534f511e/molecules-29-05314-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efe5/11596391/748bba444f57/molecules-29-05314-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efe5/11596391/b8acd984bd8c/molecules-29-05314-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efe5/11596391/3cd47d8c921d/molecules-29-05314-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efe5/11596391/8a1e5224fe9f/molecules-29-05314-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efe5/11596391/060830774cea/molecules-29-05314-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efe5/11596391/baff24616e6f/molecules-29-05314-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efe5/11596391/3cfbeb3f1c3a/molecules-29-05314-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efe5/11596391/fdb5a4163e17/molecules-29-05314-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efe5/11596391/dcab7eb305e5/molecules-29-05314-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efe5/11596391/1918ea6242ca/molecules-29-05314-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efe5/11596391/b9bbbbc7f0ab/molecules-29-05314-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efe5/11596391/d53725669009/molecules-29-05314-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efe5/11596391/e07f534f511e/molecules-29-05314-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efe5/11596391/748bba444f57/molecules-29-05314-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efe5/11596391/b8acd984bd8c/molecules-29-05314-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efe5/11596391/3cd47d8c921d/molecules-29-05314-g013.jpg

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