Mezeiova Eva, Spilovska Katarina, Nepovimova Eugenie, Gorecki Lukas, Soukup Ondrej, Dolezal Rafael, Malinak David, Janockova Jana, Jun Daniel, Kuca Kamil, Korabecny Jan
a Biomedical Research Centre, University Hospital Hradec Kralove , Hradec Kralove , Czech Republic.
b National Institute of Mental Health , Klecany , Czech Republic.
J Enzyme Inhib Med Chem. 2018 Dec;33(1):583-606. doi: 10.1080/14756366.2018.1443326.
Alzheimer's disease is debilitating neurodegenerative disorder in the elderly. Current therapy relies on administration of acetylcholinesterase inhibitors (AChEIs) -donepezil, rivastigmine, galantamine, and N-methyl-d-aspartate receptor antagonist memantine. However, their therapeutic effect is only short-term and stabilizes cognitive functions for up to 2 years. Given this drawback together with other pathological hallmarks of the disease taken into consideration, novel approaches have recently emerged to better cope with AD onset or its progression. One such strategy implies broadening the biological profile of AChEIs into so-called multi-target directed ligands (MTDLs). In this review article, we made comprehensive literature survey emphasising on donepezil template which was structurally converted into plethora of MTLDs preserving anti-cholinesterase effect and, at the same time, escalating the anti-oxidant potential, which was reported as a crucial role in the pathogenesis of the Alzheimer's disease.
阿尔茨海默病是一种使老年人衰弱的神经退行性疾病。目前的治疗方法依赖于使用乙酰胆碱酯酶抑制剂(AChEIs)——多奈哌齐、卡巴拉汀、加兰他敏,以及N-甲基-D-天冬氨酸受体拮抗剂美金刚。然而,它们的治疗效果只是短期的,最多能使认知功能稳定2年。考虑到这一缺点以及该疾病的其他病理特征,最近出现了新的方法来更好地应对阿尔茨海默病的发病或进展。其中一种策略是将AChEIs的生物学特性扩展为所谓的多靶点导向配体(MTDLs)。在这篇综述文章中,我们进行了全面的文献调查,重点关注多奈哌齐模板,该模板在结构上被转化为大量的MTLDs,保留了抗胆碱酯酶作用,同时提高了抗氧化潜力,据报道抗氧化潜力在阿尔茨海默病的发病机制中起着关键作用。