γ-Secretase Inhibitors Selected by Molecular Docking, to Develop a New Drug Against Alzheimer's Disease.

IF 1.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Carlos Humberto Trasviña-Arenas, Luis Alejandro Ayala Medina, José Luis Vique-Sánchez
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引用次数: 0

Abstract

Background: Alzheimer´s disease (AD) is one of the most common forms of dementia, is characterized by memory loss and cognitive impairment that affects more than 30 million people worldwide. The pathogenesis of Alzheimer's disease is primary driven by brain accumulation of the amyloid β peptide generated from the amyloid-β precursor protein (APP) via cleavages by β- and γ-secretase. In this study, we propose an approach by molecular docking to select compounds as γ-secretase inhibitors for decreasing the APP generation.

Methods: We selected potential γ-secretase inhibitors by molecular docking in the potential site between Asp257, Lue268, Asp385, Ile387, Phe388, and Leu432 amino acids in presenilin-1 (PS-1), using a chemical library of over 500,000 compounds.

Results: Eight compounds (AZ1 - AZ8) were selected by molecular docking to develop γ-secretase inhibitors for decreasing the APP generation.

Conclusions: AZ1 - AZ8 compounds could be interacting in the potential site between Asp257, Lue268, Asp385, Ile387, Phe388, and Leu432 amino acids in PS-1. These compounds could specifically interact in the binding pocket in PS-1 to prevent/decrease the APP generation, to develop a new drug against Alzheimer's disease.

通过分子对接筛选出的γ-分泌酶抑制剂,用于开发治疗阿尔茨海默病的新药。
背景:阿尔茨海默病(AD)是最常见的痴呆症之一,以记忆力减退和认知功能障碍为特征,影响着全球 3000 多万人。阿尔茨海默病的发病机理主要是由淀粉样β前体蛋白(APP)经β和γ-分泌酶裂解生成的淀粉样β肽在大脑中蓄积所致。在这项研究中,我们提出了一种通过分子对接选择化合物作为γ-分泌酶抑制剂以减少APP生成的方法:方法:我们利用一个包含 50 多万种化合物的化学文库,通过分子对接,在 Presenilin-1(PS-1)中 Asp257、Lue268、Asp385、Ile387、Phe388 和 Leu432 氨基酸之间的潜在位点上筛选出潜在的γ-分泌酶抑制剂:结果:通过分子对接筛选出8个化合物(AZ1 - AZ8),用于开发γ-分泌酶抑制剂,以减少APP的生成:AZ1 - AZ8化合物可与PS-1中的Asp257、Lue268、Asp385、Ile387、Phe388和Leu432氨基酸之间的潜在位点相互作用。这些化合物可以在 PS-1 的结合袋中发生特异性相互作用,从而防止/减少 APP 的生成,从而开发出一种治疗阿尔茨海默病的新药。
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来源期刊
Reports of Biochemistry and Molecular Biology
Reports of Biochemistry and Molecular Biology BIOCHEMISTRY & MOLECULAR BIOLOGY-
CiteScore
2.80
自引率
23.50%
发文量
60
审稿时长
10 weeks
期刊介绍: The Reports of Biochemistry & Molecular Biology (RBMB) is the official journal of the Varastegan Institute for Medical Sciences and is dedicated to furthering international exchange of medical and biomedical science experience and opinion and a platform for worldwide dissemination. The RBMB is a medical journal that gives special emphasis to biochemical research and molecular biology studies. The Journal invites original and review articles, short communications, reports on experiments and clinical cases, and case reports containing new insights into any aspect of biochemistry and molecular biology that are not published or being considered for publication elsewhere. Publications are accepted in the form of reports of original research, brief communications, case reports, structured reviews, editorials, commentaries, views and perspectives, letters to authors, book reviews, resources, news, and event agenda.
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