Investigação das propriedades reativas e do potencial antiparkinson através de cálculos DFT e docking molecular de alcaloides protoberberínicos de Guatteria friesiana
Autor(a) principal: | |
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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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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 |
|
_version_ |
1813274323774865408 |