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海洋生物来源的 BChE 抑制剂——综述

BChE inhibitors from marine organisms - A review.

机构信息

Department of Genetics, Federal University of Paraná, Av. Coronel Francisco Heráclito dos Santos, 210 - Jardim das Américas, 81530-001, Curitiba, PR, Brazil.

Post-graduation Program of Pharmaceutical Sciences (PPGCF), Chemical-Pharmaceutical Research Center (NIQFAR), University of Itajaí Valley (UNIVALI), R. Uruguai, 458 - Centro, 88302-901, Itajaí, SC, Brazil.

出版信息

Chem Biol Interact. 2022 Nov 1;367:110136. doi: 10.1016/j.cbi.2022.110136. Epub 2022 Sep 9.

DOI:10.1016/j.cbi.2022.110136
PMID:36096160
Abstract

Acetylcholine is a key neurotransmitter for brain and muscle function, that has its levels decreased in the brain of people with Alzheimer's Disease (AD). Cholinesterase inhibitors are medicines that decrease the breakdown of acetylcholine, through the inhibition of acetyl- and butyrylcholinesterase enzymes. Despite the fact that butyrylcholinesterase activity rises with the disease, while acetylcholinesterase activity declines, the cholinesterase inhibitors that are currently commercialized inhibit either acetylcholinesterase or both enzymes. The development of selective butyrylcholinesterase inhibitors is a promising strategy in the search for new drugs acting against AD. The marine environment is a rich source of molecules with therapeutic potential, which can provide compounds more easily than traditional methods, with reduced toxicity risks compared to synthetic molecules. This review comprises articles from 2003 to 2020, that assessed the butyrylcholinesterase inhibitory activities from marine organisms, considering their crude extracts and isolated compounds. Part of the articles reported a multi-target activity, inhibiting also other AD-related enzymes. Some of the marine compounds reported here have shown an excellent potential for butyrylcholinesterase inhibition compared to standard inhibitors. Further studies of some compounds reported here may lead to the development of a new treatment for AD.

摘要

乙酰胆碱是大脑和肌肉功能的关键神经递质,在阿尔茨海默病(AD)患者的大脑中其水平降低。胆碱酯酶抑制剂是通过抑制乙酰胆碱和丁酰胆碱酯酶来减少乙酰胆碱分解的药物。尽管事实是,随着疾病的发展,丁酰胆碱酯酶活性上升,而乙酰胆碱酯酶活性下降,但目前商业化的胆碱酯酶抑制剂要么抑制乙酰胆碱酯酶,要么同时抑制两种酶。开发选择性丁酰胆碱酯酶抑制剂是寻找针对 AD 的新药的一种有前途的策略。海洋环境是具有治疗潜力的分子的丰富来源,它可以比传统方法更容易地提供化合物,与合成分子相比,毒性风险降低。本综述包括 2003 年至 2020 年的文章,评估了海洋生物的丁酰胆碱酯酶抑制活性,考虑了它们的粗提物和分离化合物。部分文章报告了多靶点活性,还抑制了其他与 AD 相关的酶。这里报道的一些海洋化合物在丁酰胆碱酯酶抑制方面表现出了比标准抑制剂更好的潜力。对这里报道的一些化合物的进一步研究可能会导致开发新的 AD 治疗方法。

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