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探索磺胺-二氢吡啶杂合体作为阿尔茨海默病治疗多靶点配体的潜力。

Exploring the Potential of Sulfonamide-Dihydropyridine Hybrids as Multitargeted Ligands for Alzheimer's Disease Treatment.

机构信息

Laboratoire LINC UR 481, Pôle de Chimie Médicinale, Université de Franche-Comté, F-25000 Besançon, France.

Laboratory of Applied Chemistry, Heterocycles, Lipids and Polymers, Faculty of Sciences of Sfax, University of Sfax, B. P 802, Sfax 3000, Tunisia.

出版信息

Int J Mol Sci. 2023 Jun 4;24(11):9742. doi: 10.3390/ijms24119742.

DOI:10.3390/ijms24119742
PMID:37298693
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10253445/
Abstract

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease that has a heavy social and economic impact on all societies and for which there is still no cure. Multitarget-directed ligands (MTDLs) seem to be a promising therapeutic strategy for finding an effective treatment for this disease. For this purpose, new MTDLs were designed and synthesized in three steps by simple and cost-efficient procedures targeting calcium channel blockade, cholinesterase inhibition, and antioxidant activity. The biological and physicochemical results collected in this study allowed us the identification two sulfonamide-dihydropyridine hybrids showing simultaneous cholinesterase inhibition, calcium channel blockade, antioxidant capacity and Nrf2-ARE activating effect, that deserve to be further investigated for AD therapy.

摘要

阿尔茨海默病（AD）是一种多因素神经退行性疾病，给所有社会带来了沉重的社会和经济负担，目前尚无治愈方法。多靶点定向配体（MTDLs）似乎是寻找有效治疗这种疾病的一种很有前途的治疗策略。为此，我们通过简单且经济高效的程序，针对钙通道阻断、胆碱酯酶抑制和抗氧化活性，分三步设计和合成了新的 MTDLs。本研究中收集的生物学和物理化学结果使我们能够鉴定出两种磺酰胺二氢吡啶杂合体，它们同时具有胆碱酯酶抑制、钙通道阻断、抗氧化能力和 Nrf2-ARE 激活作用，值得进一步研究用于 AD 治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07b5/10253445/93d4d6f026cd/ijms-24-09742-g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07b5/10253445/7ac20b46a4e1/ijms-24-09742-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07b5/10253445/9e3bd050e947/ijms-24-09742-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07b5/10253445/c6d19d364f95/ijms-24-09742-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07b5/10253445/4f0172680584/ijms-24-09742-g003.jpg
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