Constituintes químicos de Vellozia plicata Mart.: caracterização, estudos in silico e avaliação do potencial anti-HIV-1
Autor(a) principal: | |
---|---|
Data de Publicação: | 2020 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da UFPB |
Texto Completo: | https://repositorio.ufpb.br/jspui/handle/123456789/18461 |
Resumo: | Natural products have historically been used to treat a variety of health threats and are a potential source for bioactive drugs. In this perspective, a re-study of Vellozia plicata Mart. was carried out. with the objective of isolating compounds, quantifying a chemical marker, evaluating, through studies in silico, with probability of anti-HIV activity of compounds, as well as predicting their risks of cytotoxicity, oral, intestinal absorption rate and hepatic metabolism. In addition, it investigated the cell viability and anti-HIV-1 activity of compounds and ethanolic extract. In this phytochemical study there were three compound compounds, among them amentoflavone (9), 3',8''- biisocampferide (10) and 3'-apigenin-8' '- isocaempferide (11), the latter being listed for the first time in literature. Compound (9) was proposed as a chemical marker of the species, quantified in 106.92 μg/mg of crude extract of V. plicata, with a standard deviation of less than 5%, as recommended by Resolution 899/2003 of the National Health Surveillance Agency. Biflavonoids were predicted using KNIME for the potential probability of biological activity (HIV-1), an oral absorption index and the toxicological parameters of mutagenicity and carcinogenicity. They described the ABS percentage higher than the control (36.60%) and no toxicity risks were observed within the parameters analyzed by the OSIRIS software. Predictive estimates of intestinal permeability and absorption of the three biflavonoids are >50% probable. The compounds demonstrated good MolDock Score results in molecular docking, with a better interaction between compound (9) with a protease and (10) with an integrase and reverse transcriptase. The three compounds had their structures predicted after hepatic metabolism, which include metabolic pathway in the liver to (9), if aromatic hydroxylation of cytochrome P450 enzymes has already been performed (10) and (11) greater expression of some groups has occurred aromatic and aliphatic by O-desalination, hydroxylation and carboxylation. The compounds generated from the metabolization of (9), (10) and (11) were predicted, using OSIRIS, regarding the mutagenicity and carcinogenicity capacity, however, only (9) presented a score of 29.95%, demonstrating high risk of mutagenicity. Among the compounds tested in biological studies, ethanol extract of V. plicata (71.19%) and amentoflavone (70.98%) found better cell viability compared to uninfected JLTRF - R5 cells. In assessing the anti-HIV-1 potential, no significant difference was observed between the positive control (100% DMSO), biflavonoids and ethanolic extract. In this perspective, this study demonstrates the chemical potential of V. plicata and demonstrates predictive pharmacokinetic information for biflavonoids that may assist in the process of investigation and / or development of future drugs. In addition, it highlighted the need for further investigations using other methodologies or the use of other positive controls to assess the anti-HIV-1 potential. |
id |
UFPB_05d034398b86a50d2359277deeb05201 |
---|---|
oai_identifier_str |
oai:repositorio.ufpb.br:123456789/18461 |
network_acronym_str |
UFPB |
network_name_str |
Biblioteca Digital de Teses e Dissertações da UFPB |
repository_id_str |
|
spelling |
Constituintes químicos de Vellozia plicata Mart.: caracterização, estudos in silico e avaliação do potencial anti-HIV-1Vellozia plicata Mart.3’-apigenin-8’’-isocampferídeoIn silicoAtividade anti-HIV-1VelloziaceaeAnti-HIV-1 activityCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIANatural products have historically been used to treat a variety of health threats and are a potential source for bioactive drugs. In this perspective, a re-study of Vellozia plicata Mart. was carried out. with the objective of isolating compounds, quantifying a chemical marker, evaluating, through studies in silico, with probability of anti-HIV activity of compounds, as well as predicting their risks of cytotoxicity, oral, intestinal absorption rate and hepatic metabolism. In addition, it investigated the cell viability and anti-HIV-1 activity of compounds and ethanolic extract. In this phytochemical study there were three compound compounds, among them amentoflavone (9), 3',8''- biisocampferide (10) and 3'-apigenin-8' '- isocaempferide (11), the latter being listed for the first time in literature. Compound (9) was proposed as a chemical marker of the species, quantified in 106.92 μg/mg of crude extract of V. plicata, with a standard deviation of less than 5%, as recommended by Resolution 899/2003 of the National Health Surveillance Agency. Biflavonoids were predicted using KNIME for the potential probability of biological activity (HIV-1), an oral absorption index and the toxicological parameters of mutagenicity and carcinogenicity. They described the ABS percentage higher than the control (36.60%) and no toxicity risks were observed within the parameters analyzed by the OSIRIS software. Predictive estimates of intestinal permeability and absorption of the three biflavonoids are >50% probable. The compounds demonstrated good MolDock Score results in molecular docking, with a better interaction between compound (9) with a protease and (10) with an integrase and reverse transcriptase. The three compounds had their structures predicted after hepatic metabolism, which include metabolic pathway in the liver to (9), if aromatic hydroxylation of cytochrome P450 enzymes has already been performed (10) and (11) greater expression of some groups has occurred aromatic and aliphatic by O-desalination, hydroxylation and carboxylation. The compounds generated from the metabolization of (9), (10) and (11) were predicted, using OSIRIS, regarding the mutagenicity and carcinogenicity capacity, however, only (9) presented a score of 29.95%, demonstrating high risk of mutagenicity. Among the compounds tested in biological studies, ethanol extract of V. plicata (71.19%) and amentoflavone (70.98%) found better cell viability compared to uninfected JLTRF - R5 cells. In assessing the anti-HIV-1 potential, no significant difference was observed between the positive control (100% DMSO), biflavonoids and ethanolic extract. In this perspective, this study demonstrates the chemical potential of V. plicata and demonstrates predictive pharmacokinetic information for biflavonoids that may assist in the process of investigation and / or development of future drugs. In addition, it highlighted the need for further investigations using other methodologies or the use of other positive controls to assess the anti-HIV-1 potential.Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPqCoordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESOs produtos naturais são empregados historicamente para o tratamento de diversas ameaças à saúde e são uma fonte em potencial para a obtenção de compostos bioativos. Nessa perspectiva, foi realizado um reestudo de Vellozia plicata Mart. com o objetivo de isolar compostos, quantificar um marcador químico, avaliar, por meio de estudos in silico, a probabilidade de atividade anti-HIV de compostos isolados, bem como predizer seus riscos de citotoxicidade, taxa de absorção oral, intestinal e metabolização hepática. Além disso, investigou-se a viabilidade celular e atividade anti-HIV-1 de compostos e do extrato etanólico. Nesse estudo fitoquímico foram isolados treze compostos, dentre eles a amentoflavona (9), 3’, 8’’- biisocampferídeo (10) e a 3’-apigenin-8’’-isocaempferídeo (11), sendo este último relatado pela primeira vez na literatura. O composto (9) foi proposto como marcador químico da espécie, quantificado em 106,92 μg/mg de extrato bruto de V. plicata, com desvio padrão inferior a 5%, conforme preconizado pela Resolução 899/2003 da Agência Nacional de Vigilância Sanitária). Os biflavonoides foram preditos usando o KNIME quanto a potencial probabilidade de atividade biológica (HIV-1), a taxa de absorção oral e aos parâmetros toxicológicos de mutagenicidade e carcinogenicidade. Eles apresentaram o percentual ABS superior ao controle (36,60%) e não foram observados riscos de toxicidade dentro dos parâmetros analisados pelo software OSIRIS. As análises preditivas de permeabilidade e absorção intestinal dos três biflavonoides isolados apresentaram probabilidade > 50%. Os compostos demonstraram bons resultados MolDock Score no docking molecular, ocorrendo melhor interação entre o composto (9) com a protease, e o (10) com a integrase e transcriptase reversa. Os três compostos tiveram suas estruturas preditas após metabolização hepática, indicando que a via metabólica no fígado para (9) se daria pela hidroxilação aromática das enzimas do citocromo P450, já nos compostos (10) e (11) ocorre uma maior expressão de alguns grupos aromáticos e alifáticos por Odesalquilação, hidroxilação e carboxilação. Os compostos gerados a partir da metabolização de (9), (10) e (11) foram preditos, utilizando o OSIRIS, quanto a capacidade de mutagenicidade e carcinogenicidade, entretanto, apenas o (9) apresentou um score de 29,95%, demostrando alto risco de mutagenicidade. Dentre os compostos testados nos estudos biológicos, o extrato etanólico de V. plicata (71,19%) e a amentoflavona (70,98%) apresentaram melhor viabilidade celular frente as células JLTRF – R5 não infectadas. Na avaliação do potencial anti-HIV-1 não foi observado diferença significativa entre o controle positivo (DMSO 100%), os biflavonoides e o extrato etanólico. Nessa perspectiva, este reestudo demonstrou o potencial químico de V. plicata e demonstou informações farmacocinéticas preditivas dos biflavonoides que poderão auxiliar no processo de investigação e/desenvolvimento de futuros fármacos. Além disso, evidenciou a necessidade de novas investigação por outras metodologias ou utilizando outros controles positivos para avaliar o potencial anti-HIV-1.Universidade Federal da ParaíbaBrasilFarmacologiaPrograma de Pós-Graduação em Produtos Naturais e Sintéticos BioativosUFPBSilva, Marcelo Sobral dahttp://lattes.cnpq.br/5980170934785365Pinheiro, Anderson Angel Vieira2020-11-19T12:54:37Z2020-07-202020-11-19T12:54:37Z2020-02-27info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesishttps://repositorio.ufpb.br/jspui/handle/123456789/18461porhttp://creativecommons.org/licenses/by-nd/3.0/br/info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFPBinstname:Universidade Federal da Paraíba (UFPB)instacron:UFPB2021-09-13T19:45:43Zoai:repositorio.ufpb.br:123456789/18461Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufpb.br/PUBhttp://tede.biblioteca.ufpb.br:8080/oai/requestdiretoria@ufpb.br|| diretoria@ufpb.bropendoar:2021-09-13T19:45:43Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)false |
dc.title.none.fl_str_mv |
Constituintes químicos de Vellozia plicata Mart.: caracterização, estudos in silico e avaliação do potencial anti-HIV-1 |
title |
Constituintes químicos de Vellozia plicata Mart.: caracterização, estudos in silico e avaliação do potencial anti-HIV-1 |
spellingShingle |
Constituintes químicos de Vellozia plicata Mart.: caracterização, estudos in silico e avaliação do potencial anti-HIV-1 Pinheiro, Anderson Angel Vieira Vellozia plicata Mart. 3’-apigenin-8’’-isocampferídeo In silico Atividade anti-HIV-1 Velloziaceae Anti-HIV-1 activity CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
title_short |
Constituintes químicos de Vellozia plicata Mart.: caracterização, estudos in silico e avaliação do potencial anti-HIV-1 |
title_full |
Constituintes químicos de Vellozia plicata Mart.: caracterização, estudos in silico e avaliação do potencial anti-HIV-1 |
title_fullStr |
Constituintes químicos de Vellozia plicata Mart.: caracterização, estudos in silico e avaliação do potencial anti-HIV-1 |
title_full_unstemmed |
Constituintes químicos de Vellozia plicata Mart.: caracterização, estudos in silico e avaliação do potencial anti-HIV-1 |
title_sort |
Constituintes químicos de Vellozia plicata Mart.: caracterização, estudos in silico e avaliação do potencial anti-HIV-1 |
author |
Pinheiro, Anderson Angel Vieira |
author_facet |
Pinheiro, Anderson Angel Vieira |
author_role |
author |
dc.contributor.none.fl_str_mv |
Silva, Marcelo Sobral da http://lattes.cnpq.br/5980170934785365 |
dc.contributor.author.fl_str_mv |
Pinheiro, Anderson Angel Vieira |
dc.subject.por.fl_str_mv |
Vellozia plicata Mart. 3’-apigenin-8’’-isocampferídeo In silico Atividade anti-HIV-1 Velloziaceae Anti-HIV-1 activity CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
topic |
Vellozia plicata Mart. 3’-apigenin-8’’-isocampferídeo In silico Atividade anti-HIV-1 Velloziaceae Anti-HIV-1 activity CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
description |
Natural products have historically been used to treat a variety of health threats and are a potential source for bioactive drugs. In this perspective, a re-study of Vellozia plicata Mart. was carried out. with the objective of isolating compounds, quantifying a chemical marker, evaluating, through studies in silico, with probability of anti-HIV activity of compounds, as well as predicting their risks of cytotoxicity, oral, intestinal absorption rate and hepatic metabolism. In addition, it investigated the cell viability and anti-HIV-1 activity of compounds and ethanolic extract. In this phytochemical study there were three compound compounds, among them amentoflavone (9), 3',8''- biisocampferide (10) and 3'-apigenin-8' '- isocaempferide (11), the latter being listed for the first time in literature. Compound (9) was proposed as a chemical marker of the species, quantified in 106.92 μg/mg of crude extract of V. plicata, with a standard deviation of less than 5%, as recommended by Resolution 899/2003 of the National Health Surveillance Agency. Biflavonoids were predicted using KNIME for the potential probability of biological activity (HIV-1), an oral absorption index and the toxicological parameters of mutagenicity and carcinogenicity. They described the ABS percentage higher than the control (36.60%) and no toxicity risks were observed within the parameters analyzed by the OSIRIS software. Predictive estimates of intestinal permeability and absorption of the three biflavonoids are >50% probable. The compounds demonstrated good MolDock Score results in molecular docking, with a better interaction between compound (9) with a protease and (10) with an integrase and reverse transcriptase. The three compounds had their structures predicted after hepatic metabolism, which include metabolic pathway in the liver to (9), if aromatic hydroxylation of cytochrome P450 enzymes has already been performed (10) and (11) greater expression of some groups has occurred aromatic and aliphatic by O-desalination, hydroxylation and carboxylation. The compounds generated from the metabolization of (9), (10) and (11) were predicted, using OSIRIS, regarding the mutagenicity and carcinogenicity capacity, however, only (9) presented a score of 29.95%, demonstrating high risk of mutagenicity. Among the compounds tested in biological studies, ethanol extract of V. plicata (71.19%) and amentoflavone (70.98%) found better cell viability compared to uninfected JLTRF - R5 cells. In assessing the anti-HIV-1 potential, no significant difference was observed between the positive control (100% DMSO), biflavonoids and ethanolic extract. In this perspective, this study demonstrates the chemical potential of V. plicata and demonstrates predictive pharmacokinetic information for biflavonoids that may assist in the process of investigation and / or development of future drugs. In addition, it highlighted the need for further investigations using other methodologies or the use of other positive controls to assess the anti-HIV-1 potential. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-11-19T12:54:37Z 2020-07-20 2020-11-19T12:54:37Z 2020-02-27 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://repositorio.ufpb.br/jspui/handle/123456789/18461 |
url |
https://repositorio.ufpb.br/jspui/handle/123456789/18461 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
http://creativecommons.org/licenses/by-nd/3.0/br/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
http://creativecommons.org/licenses/by-nd/3.0/br/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal da Paraíba Brasil Farmacologia Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos UFPB |
publisher.none.fl_str_mv |
Universidade Federal da Paraíba Brasil Farmacologia Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos UFPB |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações da UFPB instname:Universidade Federal da Paraíba (UFPB) instacron:UFPB |
instname_str |
Universidade Federal da Paraíba (UFPB) |
instacron_str |
UFPB |
institution |
UFPB |
reponame_str |
Biblioteca Digital de Teses e Dissertações da UFPB |
collection |
Biblioteca Digital de Teses e Dissertações da UFPB |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB) |
repository.mail.fl_str_mv |
diretoria@ufpb.br|| diretoria@ufpb.br |
_version_ |
1801843016746401792 |