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近期合成香豆素类作为 MAO-B 抑制剂的研究进展及构效关系研究:更新综述。

Recent Advancements and SAR Studies of Synthetic Coumarins as MAO-B Inhibitors: An Updated Review.

机构信息

Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Moga, Punjab, 142001, India.

Chitkara School of Pharmacy, Chitkara University, Baddi, Himachal Pradesh, 174103, India.

出版信息

Mini Rev Med Chem. 2024;24(20):1834-1846. doi: 10.2174/0113895575290599240503080025.

Abstract

BACKGROUND

The oxidative deamination of a wide range of endogenous and exogenous amines is catalyzed by a family of enzymes known as monoamine oxidases (MAOs), which are reliant on flavin-adenine dinucleotides. Numerous neurological conditions, such as Parkinson's disease (PD) and Alzheimer's disease (AD), are significantly correlated with changes in the amounts of biogenic amines in the brain caused by MAO. Hydrogen peroxide, reactive oxygen species, and ammonia, among other toxic consequences of this oxidative breakdown, can harm brain cells' mitochondria and cause oxidative damage.

OBJECTIVE

The prime objective of this review article was to highlight and conclude the recent advancements in structure-activity relationships of synthetic derivatives of coumarins for MAO-B inhibition, published in the last five years' research articles.

METHODS

The literature (between 2019 and 2023) was searched from platforms like Science Direct, Google Scholar, PubMed, etc. After going through the literature, we have found a number of coumarin derivatives being synthesized by researchers for the inhibition of MAO-B for the management of diseases associated with the enzyme such as Alzheimer's Disease and Parkinson's Disease. The effect of these coumarin derivatives on the enzyme depends on the substitutions associated with the structure. The structure-activity relationships of the synthetic coumarin derivatives that are popular nowadays have been described and summarized in the current study.

RESULTS

The results revealed the updated review on SAR studies of synthetic coumarins as MAO-B inhibitors, specifically for Alzheimer's Disease and Parkinson's Disease. The patents reported on coumarin derivatives as MAO-B inhibitors were also highlighted.

CONCLUSION

Recently, coumarins, a large class of chemicals with both natural and synthetic sources, have drawn a lot of attention because of the vast range of biological actions they have that are linked to neurological problems. Numerous studies have demonstrated that chemically produced and naturally occurring coumarin analogs both exhibited strong MAO-B inhibitory action. Coumarins bind to MAO-B reversibly thereby preventing the breakdown of neurotransmitters like dopamine leading to the inhibition of the enzyme A number of MAO-B blockers have been proven to be efficient therapies for treating neurological diseases like Alzheimer's Disease and Parkinson's Disease. To combat these illnesses, there is still an urgent need to find effective treatment compounds.

摘要

背景

广泛的内源性和外源性胺的氧化脱氨是由单胺氧化酶(MAO)家族的酶催化的,这些酶依赖黄素腺嘌呤二核苷酸。许多神经疾病,如帕金森病(PD)和阿尔茨海默病(AD),与 MAO 引起的大脑中生物胺含量的变化显著相关。这种氧化分解的其他毒性后果,如过氧化氢、活性氧和氨,会损害脑细胞的线粒体并导致氧化损伤。

目的

本综述文章的主要目的是强调和总结过去五年研究文章中发表的香豆素合成衍生物对 MAO-B 抑制的构效关系的最新进展。

方法

文献(2019 年至 2023 年)从 Science Direct、Google Scholar、PubMed 等平台进行搜索。在阅读文献后,我们发现研究人员合成了许多香豆素衍生物,用于抑制 MAO-B,以治疗与该酶相关的疾病,如阿尔茨海默病和帕金森病。这些香豆素衍生物对酶的影响取决于与结构相关的取代基。本研究描述并总结了目前流行的合成香豆素衍生物的构效关系。

结果

结果揭示了作为 MAO-B 抑制剂的合成香豆素的 SAR 研究的最新综述,特别是针对阿尔茨海默病和帕金森病。还强调了报道的作为 MAO-B 抑制剂的香豆素衍生物专利。

结论

最近,香豆素作为一个具有天然和合成来源的大型化学物质家族,由于其与神经问题相关的广泛的生物作用而引起了很多关注。许多研究表明,化学合成和天然存在的香豆素类似物都表现出强烈的 MAO-B 抑制作用。香豆素与 MAO-B 可逆结合,从而防止多巴胺等神经递质的分解,从而抑制酶的活性。许多 MAO-B 抑制剂已被证明是治疗阿尔茨海默病和帕金森病等神经疾病的有效疗法。为了治疗这些疾病,仍然迫切需要找到有效的治疗化合物。

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