Theoretical Study of Monoamine Oxidase B Inhibitors as Drug Candidates for Treatment of Parkinson's Disease.

Q3 Psychology

Central nervous system agents in medicinal chemistry Pub Date : 2020-01-01 DOI:10.2174/1871524920666200217110211

Lucilene R Souza, Leide C S Picanço, Maiara F B Brito, Marcos R S Almeida, Bianca L B Marino, Kessia P A Sousa, Jaderson V Ferreira, Cleydson B R Dos Santos, Guilherme M Silva, Carlos H T P Silva, Carlton A Taft, Lorane I S Hage-Melim

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引用次数: 1

Abstract

Background: Drugs used for Parkinson's disease (PD) are mainly responsible for only relieving major symptoms, but may present several side effects that are typical of such pharmacological treatment.

Methods: This study aimed to use in silico methods for drug designing inhibitors of the PD therapeutic target, monoamine oxidase B (MAO-B). Thus, 20 MAO-B inhibitors from the BindingDB database were selected followed by a calculation of their descriptors at DFT B3LYP/6-31G** level of theory.

Results: Statistical analysis considering a Pearson correlation matrix led to the selection of electrophilicity index as a descriptor related to the biological activity of inhibitors. Furthermore, based on the prediction of suitable ADME/Tox properties, the molecule CID 54583085 was selected as a template to carry out structural modifications to obtain 3 analogues, whereas molecules B and C showed significant improvement in mutagenicity and carcinogenicity, in relation to the template.

Conclusion: Thus, it is concluded that the proposed modifications led us to satisfactory results, since there was an improvement in the toxicological properties of molecules, however, further studies must be carried out to evaluate their biological activities as possible MAO-B inhibitors for PD treatment.

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单胺氧化酶B抑制剂作为治疗帕金森病候选药物的理论研究

背景:用于帕金森病(PD)的药物主要只负责缓解主要症状，但可能存在一些典型的此类药物治疗的副作用。结果:考虑Pearson相关矩阵的统计分析导致选择亲电性指数作为抑制剂生物活性的描述符。此外，在预测合适的ADME/Tox性质的基础上，选择分子CID 54583085作为模板进行结构修饰，得到3个类似物，而分子B和C的致突变性和致癌性相对于模板有显著提高。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Central nervous system agents in medicinal chemistry Psychology-Neuropsychology and Physiological Psychology

CiteScore

2.10

自引率

0.00%

发文量

期刊介绍： Central Nervous System Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of new central nervous system agents. Containing a series of timely in-depth reviews written by leaders in the field covering a range of current topics, Central Nervous System Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in the field.