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

[ Vol. 20 , Issue. 2 ]

Author(s):

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 and Lorane I.S. Hage-Melim*   Pages 128 - 143 ( 16 )

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.

Keywords:

MAO-B inhibitors, Parkinson’s disease, MEP, pharmacokinetic, toxicological properties, QSAR.

Affiliation:

Laboratory of Pharmaceutical and Medicinal Chemistry (PharMedChem), Federal University of Amapa, Macapa, Amapa, Laboratory of Pharmaceutical and Medicinal Chemistry (PharMedChem), Federal University of Amapa, Macapa, Amapa, Laboratory of Pharmaceutical and Medicinal Chemistry (PharMedChem), Federal University of Amapa, Macapa, Amapa, Laboratory of Pharmaceutical and Medicinal Chemistry (PharMedChem), Federal University of Amapa, Macapa, Amapa, Laboratory of Pharmaceutical and Medicinal Chemistry (PharMedChem), Federal University of Amapa, Macapa, Amapa, Laboratory of Pharmaceutical and Medicinal Chemistry (PharMedChem), Federal University of Amapa, Macapa, Amapa, Laboratory of Pharmaceutical and Medicinal Chemistry (PharMedChem), Federal University of Amapa, Macapa, Amapa, Laboratory of Modeling and Computational Chemistry, Federal University of Amapa, Macapa, Amapa, Computational Laboratory of Pharmaceutical Chemistry, School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Computational Laboratory of Pharmaceutical Chemistry, School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazilian Center for Physics Research, Rio de Janeiro, Rio de Janeiro, Laboratory of Pharmaceutical and Medicinal Chemistry (PharMedChem), Federal University of Amapa, Macapa, Amapa

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