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新型金刚烷胺与咔唑衍生物的缀合物作为 AD 治疗的潜在多靶标药物。

Novel conjugates of aminoadamantanes with carbazole derivatives as potential multitarget agents for AD treatment.

机构信息

Institute of Physiologically Active Compounds Russian Academy of Sciences, Chernogolovka, 142432, Russia.

Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Moscow, 119334, Russia.

出版信息

Sci Rep. 2017 Mar 30;7:45627. doi: 10.1038/srep45627.

Abstract

A new group of compounds, promising for the design of original multitarget therapeutic agents for treating neurodegenerative diseases, based on conjugates of aminoadamantane and carbazole derivatives was synthesized and investigated. Compounds of these series were found to interact with a group of targets that play an important role in the development of this type of diseases. First of all, these compounds selectively inhibit butyrylcholinesterase, block NMDA receptors containing NR2B subunits while maintaining the properties of MK-801 binding site blockers, exert microtubules stabilizing properties, and possess the ability to protect nerve cells from death at the calcium overload conditions. The leading compound C-2h has been shown the most promising effects on all analyzed parameters. Thus, these compounds can be regarded as promising candidates for the design of multi-target disease-modifying drugs for treatment of AD and/or similar neuropathologies.

摘要

一组新的化合物,基于金刚烷和咔唑衍生物的缀合物,有望用于设计治疗神经退行性疾病的新型多靶治疗剂,已经被合成并进行了研究。这些系列的化合物被发现与一组在这类疾病发展中起重要作用的靶点相互作用。首先,这些化合物选择性地抑制丁酰胆碱酯酶,阻断含有 NR2B 亚基的 NMDA 受体,同时保持 MK-801 结合位点抑制剂的特性,发挥微管稳定特性,并具有在钙超载条件下保护神经细胞免于死亡的能力。先导化合物 C-2h 在所有分析参数上都显示出最有前途的效果。因此,这些化合物可以被视为设计用于治疗 AD 和/或类似神经病理学的多靶疾病修饰药物的有前途的候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7f1/5372361/eacb12924c08/srep45627-f1.jpg

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