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
{"title":"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","authors":"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","doi":"10.2174/1871524920666200217110211","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":9799,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":"20 2","pages":"128-143"},"PeriodicalIF":0.0000,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Theoretical Study of Monoamine Oxidase B Inhibitors as Drug Candidates for Treatment of Parkinson's Disease.\",\"authors\":\"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\",\"doi\":\"10.2174/1871524920666200217110211\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>Statistical analysis considering a Pearson correlation matrix led to the selection of electrophilicity index as a descriptor related to the biological activity of inhibitors. 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Theoretical Study of Monoamine Oxidase B Inhibitors as Drug Candidates for Treatment of Parkinson's Disease.
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.
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.
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