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含吡唑啉化合物作为神经退行性疾病的治疗靶点

Pyrazoline Containing Compounds as Therapeutic Targets for Neurodegenerative Disorders.

作者信息

Ahsan Mohamed Jawed, Ali Amena, Ali Abuzer, Thiriveedhi Arunkumar, Bakht Mohammed A, Yusuf Mohammad, Afzal Obaid, Altamimi Abdulmalik Saleh Alfawaz

机构信息

Department of Pharmaceutical Chemistry, Maharishi Arvind College of Pharmacy, Jaipur, Rajasthan 302 039, India.

Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.

出版信息

ACS Omega. 2022 Oct 17;7(43):38207-38245. doi: 10.1021/acsomega.2c05339. eCollection 2022 Nov 1.

Abstract

Pyrazolines are a significant class of heterocyclic compounds with essential biological activities. They are quite stable, which has inspired medicinal chemists to experiment with the ring's structure in many different ways to create a variety of pharmacological activities. The structures of numerous commercially available therapeutic agents contain a pyrazoline ring. Pyrazolines are well-known for their ability to treat neurodegenerative diseases. The neurodegenerative diseases that affect huge populations globally include Alzheimer's disease (AD), Parkinson's disease (PD), and psychiatric disorders. The neuroprotective properties of pyrazolines published since 2003 are covered in the current review. Structure-activity relationships (SARs), molecular docking simulation, anticholinesterase (anti-AChE), and monoamine oxidase (MAO A/B) inhibitory actions are all covered in this article. Pyrazolines were discovered to have beneficial effects in the management of AD and were revealed to be inhibitors of acetylcholine esterase (AChE) and beta-amyloid (A) plaques. They were discovered to be efficient against PD and also targeted MAO B and COMT. It was discovered that the pyrazolines block MAO A to treat psychiatric diseases. Pyrazolines are significant heteroaromatic scaffolds with a variety of biological functions. They were discovered to be remarkably stable and serve as an indispensable anchor for the development of new drugs. By blocking AChE and MAOs, they may be used to treat neurodegenerative diseases. The discussion outlined here is an essential and helpful resource for medicinal chemists who are investigating and applying pyrazolines in neurodegenerative research initiatives as well as to expedite future research programs on neurodegenerative disorders.

摘要

吡唑啉是一类具有重要生物活性的杂环化合物。它们相当稳定,这激发了药物化学家以多种不同方式对该环结构进行实验,以创造出各种药理活性。许多市售治疗剂的结构都含有吡唑啉环。吡唑啉以其治疗神经退行性疾病的能力而闻名。全球影响大量人群的神经退行性疾病包括阿尔茨海默病(AD)、帕金森病(PD)和精神疾病。本综述涵盖了自2003年以来发表的吡唑啉的神经保护特性。本文还讨论了构效关系(SARs)、分子对接模拟、抗胆碱酯酶(anti-AChE)和单胺氧化酶(MAO A/B)抑制作用。研究发现吡唑啉在AD的治疗中具有有益作用,并且被揭示为乙酰胆碱酯酶(AChE)和β-淀粉样蛋白(A)斑块的抑制剂。它们被发现对PD有效,并且还靶向MAO B和儿茶酚-O-甲基转移酶(COMT)。研究发现吡唑啉通过阻断MAO A来治疗精神疾病。吡唑啉是具有多种生物学功能的重要杂芳基支架。它们被发现非常稳定,并且是新药开发中不可或缺的基础。通过阻断AChE和MAOs,它们可用于治疗神经退行性疾病。这里概述的讨论对于正在神经退行性研究项目中研究和应用吡唑啉的药物化学家来说是一份重要且有用的资源,同时也有助于加快未来关于神经退行性疾病的研究计划。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9359/9631758/212d8c661d23/ao2c05339_0001.jpg

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