Investigação das propriedades reativas e do potencial antiparkinson através de cálculos DFT e docking molecular de alcaloides protoberberínicos de Guatteria friesiana

Detalhes bibliográficos
Autor(a) principal: Tananta, Victor Lima
Data de Publicação: 2023
Tipo de documento: Trabalho de conclusão de curso
Idioma: por
Título da fonte: Repositório Institucional da UFAM
Texto Completo: http://riu.ufam.edu.br/handle/prefix/7179
Resumo: The present work addresses the computational theoretical study of the protoberberine alkaloids 13-hydroxy-discretinine and 7,8-dihydro-8-hydroxypalmatine, previously isolated from the plant of Guatteria friesiana genus, employing the density functional theory (DFT) to analyze their electronic and pharmacological properties. Using the Gaussian 09 software, the frontier molecular orbitals HOMO and LUMO, global reactivity indices (hardness, chemical potential, electronegativity, and electrophilicity index), local reactivity indices (Fukui indices), as well as the electrostatic potential maps (ESP) and average local ionization energy (ALIE) using the Multiwfn program were obtained at the B3LYP-D3(BJ)/6-311++G(2df, 2pd) revealed that the alkaloids exhibit distinct reactivities, with nucleophilic and electrophilic sites located on rings A, D (13-hydroxy-discretinine) and rings B, C (7,8-dihydro-8-hydroxypalmatine). Solvation free energies calculated for both alkaloids using: water, acetone, dichloromethane, and metanol; it was revealed that they have higher solubility in dichloromethane. Finally, using the Autodock Vina software, molecular docking calculations with human serum albumin (HSA), responsible for drug transport in the bloodstream, as well as the monoamine oxidase A (MAO-A) and B (MAO-B) enzymes, target enzymes in the treatment of Parkinson's disease, were evaluated, indicating that the alkaloids preferentially inhibit MAO-B (-8.0 and 5.7 kcal/mol) and form complexes with HSA, exhibiting docking energies of -8.5 and -8.1 kcal/mol. These results support that such alkaloids are potential candidates for the treatment of Parkinson's disease.
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spelling Investigação das propriedades reativas e do potencial antiparkinson através de cálculos DFT e docking molecular de alcaloides protoberberínicos de Guatteria friesianaAlcaloides protoberberínicosTeoria do funcional de densidadeDocking MolecularDoença de ParkinsonMonoamina oxidaseCIENCIAS EXATAS E DA TERRA: QUIMICAParkinson, Doença de - TratamentoParkinson, Doença de - Aspectos molecularesThe present work addresses the computational theoretical study of the protoberberine alkaloids 13-hydroxy-discretinine and 7,8-dihydro-8-hydroxypalmatine, previously isolated from the plant of Guatteria friesiana genus, employing the density functional theory (DFT) to analyze their electronic and pharmacological properties. Using the Gaussian 09 software, the frontier molecular orbitals HOMO and LUMO, global reactivity indices (hardness, chemical potential, electronegativity, and electrophilicity index), local reactivity indices (Fukui indices), as well as the electrostatic potential maps (ESP) and average local ionization energy (ALIE) using the Multiwfn program were obtained at the B3LYP-D3(BJ)/6-311++G(2df, 2pd) revealed that the alkaloids exhibit distinct reactivities, with nucleophilic and electrophilic sites located on rings A, D (13-hydroxy-discretinine) and rings B, C (7,8-dihydro-8-hydroxypalmatine). Solvation free energies calculated for both alkaloids using: water, acetone, dichloromethane, and metanol; it was revealed that they have higher solubility in dichloromethane. Finally, using the Autodock Vina software, molecular docking calculations with human serum albumin (HSA), responsible for drug transport in the bloodstream, as well as the monoamine oxidase A (MAO-A) and B (MAO-B) enzymes, target enzymes in the treatment of Parkinson's disease, were evaluated, indicating that the alkaloids preferentially inhibit MAO-B (-8.0 and 5.7 kcal/mol) and form complexes with HSA, exhibiting docking energies of -8.5 and -8.1 kcal/mol. These results support that such alkaloids are potential candidates for the treatment of Parkinson's disease.O presente trabalho aborda o estudo teórico computacional dos alcaloides protoberberínicos 13-hidroxi-discretinina e 7,8-diidro-8-hidroxipalmatina, precedentemente isolados da planta do gênero Guatteria friesiana, empregando a teoria do funcional de densidade (TFD) para analisar suas propriedades eletrônicas e farmacológicas. Utilizando o softwate Gaussian 09, os orbitais moleculares de fronteira HOMO e LUMO, índices de reatividade global (dureza, potencial químico, eletronegatividade, e índice de eletrofilicidade), índices de reatividade local (índices de Fukui), assim como os mapas de potencial eletrostático (MPE) e energia de ionização média local (EIML) utilizando o programa Multiwfn obtidos em nível de teoria B3LYP-D3(BJ)/6-311++G(2df, 2pd), revelaram que os alcaloides possuem reatividades distintas, onde os sítios nucleofílicos e eletrofílicos estavam sobre os anéis A, D (13-hidroxi-discretinina) e B, C (7,8-diidro-8-hidroxipalmatina). Através das energias livres de solvatação, calculadas para ambos os alcaloides utilizando os solventes: água, acetona, diclorometano e metanol; foi revelado que possuem maior solubilidade em diclorometano. Por fim, utilizando o software Autodock Vina, cálculos de docking molecular com a albumina sérica humana (ASH), responsável pelo transporte de drogas na corrente sanguínea, bem como as enzimas monoamina oxidases A (MAO-A) e B (MAO-B), enzimas alvo no tratamento da doença de Parkinson, foram realizados, indicando que os alcaloides inibem preferencialmente a MAO-B (-8,0 e 5,7 kcal/mol) e complexam com a ASH exibindo energias de docagem de -8,5 e -8,1 kcal/mol. Tais resultados sustentam que os alcaloides em questão são possíveis candidatos para o tratamento da doença de Parkinson.2NãoBrasilICE - Instituto de Ciências ExatasManaus (AM)Química - Bacharelado - ManausCosta, Renyer Alveshttp://lattes.cnpq.br/8238411816105938Braga, Neila de AlmeidaMachado, Marcos BatistaTananta, Victor Lima2023-11-13T12:29:06Z2023-11-13T12:29:06Z2023-07-07info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/bachelorThesishttp://riu.ufam.edu.br/handle/prefix/7179porhttps://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFAMinstname:Universidade Federal do Amazonas (UFAM)instacron:UFAM2023-11-13T12:30:02Zoai:localhost:prefix/7179Repositório InstitucionalPUBhttp://riu.ufam.edu.br/oai/requestopendoar:2023-11-13T12:30:02Repositório Institucional da UFAM - Universidade Federal do Amazonas (UFAM)false
dc.title.none.fl_str_mv Investigação das propriedades reativas e do potencial antiparkinson através de cálculos DFT e docking molecular de alcaloides protoberberínicos de Guatteria friesiana
title Investigação das propriedades reativas e do potencial antiparkinson através de cálculos DFT e docking molecular de alcaloides protoberberínicos de Guatteria friesiana
spellingShingle Investigação das propriedades reativas e do potencial antiparkinson através de cálculos DFT e docking molecular de alcaloides protoberberínicos de Guatteria friesiana
Tananta, Victor Lima
Alcaloides protoberberínicos
Teoria do funcional de densidade
Docking Molecular
Doença de Parkinson
Monoamina oxidase
CIENCIAS EXATAS E DA TERRA: QUIMICA
Parkinson, Doença de - Tratamento
Parkinson, Doença de - Aspectos moleculares
title_short Investigação das propriedades reativas e do potencial antiparkinson através de cálculos DFT e docking molecular de alcaloides protoberberínicos de Guatteria friesiana
title_full Investigação das propriedades reativas e do potencial antiparkinson através de cálculos DFT e docking molecular de alcaloides protoberberínicos de Guatteria friesiana
title_fullStr Investigação das propriedades reativas e do potencial antiparkinson através de cálculos DFT e docking molecular de alcaloides protoberberínicos de Guatteria friesiana
title_full_unstemmed Investigação das propriedades reativas e do potencial antiparkinson através de cálculos DFT e docking molecular de alcaloides protoberberínicos de Guatteria friesiana
title_sort Investigação das propriedades reativas e do potencial antiparkinson através de cálculos DFT e docking molecular de alcaloides protoberberínicos de Guatteria friesiana
author Tananta, Victor Lima
author_facet Tananta, Victor Lima
author_role author
dc.contributor.none.fl_str_mv Costa, Renyer Alves
http://lattes.cnpq.br/8238411816105938
Braga, Neila de Almeida
Machado, Marcos Batista
dc.contributor.author.fl_str_mv Tananta, Victor Lima
dc.subject.por.fl_str_mv Alcaloides protoberberínicos
Teoria do funcional de densidade
Docking Molecular
Doença de Parkinson
Monoamina oxidase
CIENCIAS EXATAS E DA TERRA: QUIMICA
Parkinson, Doença de - Tratamento
Parkinson, Doença de - Aspectos moleculares
topic Alcaloides protoberberínicos
Teoria do funcional de densidade
Docking Molecular
Doença de Parkinson
Monoamina oxidase
CIENCIAS EXATAS E DA TERRA: QUIMICA
Parkinson, Doença de - Tratamento
Parkinson, Doença de - Aspectos moleculares
description The present work addresses the computational theoretical study of the protoberberine alkaloids 13-hydroxy-discretinine and 7,8-dihydro-8-hydroxypalmatine, previously isolated from the plant of Guatteria friesiana genus, employing the density functional theory (DFT) to analyze their electronic and pharmacological properties. Using the Gaussian 09 software, the frontier molecular orbitals HOMO and LUMO, global reactivity indices (hardness, chemical potential, electronegativity, and electrophilicity index), local reactivity indices (Fukui indices), as well as the electrostatic potential maps (ESP) and average local ionization energy (ALIE) using the Multiwfn program were obtained at the B3LYP-D3(BJ)/6-311++G(2df, 2pd) revealed that the alkaloids exhibit distinct reactivities, with nucleophilic and electrophilic sites located on rings A, D (13-hydroxy-discretinine) and rings B, C (7,8-dihydro-8-hydroxypalmatine). Solvation free energies calculated for both alkaloids using: water, acetone, dichloromethane, and metanol; it was revealed that they have higher solubility in dichloromethane. Finally, using the Autodock Vina software, molecular docking calculations with human serum albumin (HSA), responsible for drug transport in the bloodstream, as well as the monoamine oxidase A (MAO-A) and B (MAO-B) enzymes, target enzymes in the treatment of Parkinson's disease, were evaluated, indicating that the alkaloids preferentially inhibit MAO-B (-8.0 and 5.7 kcal/mol) and form complexes with HSA, exhibiting docking energies of -8.5 and -8.1 kcal/mol. These results support that such alkaloids are potential candidates for the treatment of Parkinson's disease.
publishDate 2023
dc.date.none.fl_str_mv 2023-11-13T12:29:06Z
2023-11-13T12:29:06Z
2023-07-07
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/bachelorThesis
format bachelorThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://riu.ufam.edu.br/handle/prefix/7179
url http://riu.ufam.edu.br/handle/prefix/7179
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv https://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Brasil
ICE - Instituto de Ciências Exatas
Manaus (AM)
Química - Bacharelado - Manaus
publisher.none.fl_str_mv Brasil
ICE - Instituto de Ciências Exatas
Manaus (AM)
Química - Bacharelado - Manaus
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFAM
instname:Universidade Federal do Amazonas (UFAM)
instacron:UFAM
instname_str Universidade Federal do Amazonas (UFAM)
instacron_str UFAM
institution UFAM
reponame_str Repositório Institucional da UFAM
collection Repositório Institucional da UFAM
repository.name.fl_str_mv Repositório Institucional da UFAM - Universidade Federal do Amazonas (UFAM)
repository.mail.fl_str_mv
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