Análise estereoquímica dos alcaloides piperidínicos isolados de Senna spectabilis e avaliação do potencial anticolinesterásico

Detalhes bibliográficos
Autor(a) principal: Novais, Raul Marques
Data de Publicação: 2019
Tipo de documento: Trabalho de conclusão de curso
Idioma: por
Título da fonte: Repositório Institucional da UFU
Texto Completo: https://repositorio.ufu.br/handle/123456789/28461
Resumo: Natural products have been used since ancient times as a way to cure or prevent human illness. Throughout history, compounds obtained from natural sources have aroused great interest due to the complexity of molecular arrangements associated with the three-dimensional dispositions of asymmetric carbons and your biological activities. Thus, for a long time, synthetic drugs were inspired by the structures of natural compounds, frequently chirals, which were produced in the form of racemates, ignoring the possible differences in biological activity that different stereoisomers could cause. Against this background, we have invested in the study of piperidine alkaloids present in Senna spectabilis, which have stereogenic centers and verified action on the central nervous system, as well as presenting various biological activities such as leishmanicide, antimalarial and anticholinesterase. In this sense, the present study describes the isolation process of chiral piperidine alkaloids from the ethanolic extract of Senna spectabilis flowers. This extract was submitted to liquid-liquid extraction with hexane and dichloromethane, being the second fraction with the highest concentration of alkaloids. This fraction was submitted to different chromatographic procedures, from which homologues 1 and 2, previously described in S. spectabilis, were isolated, as well as the two new homologous compounds, whose chromatographic and spectrometric analyzes indicate that they are diastereoisomers of 1 and 2. Then, the mixture containing 4 and 5 was subjected to an esterification reaction with acetyl chloride, obtaining compound 60. The natural and semi-synthetic compounds were evaluated in the acetylcholinesterase (AChE) inhibition test, where it was possible to observe that homologous alkaloids 1 (IC50 0.62 ± 0.01 ug/mL) and 2 (IC50 0.87 ± 0.12 ug/mL), with the same stereochemistry are more potent than the respective stereoisomers 4 (IC50 6.49 ± 0.23 ug/mL) and 5 (IC50 17.60 ± 1.90 ug/mL). These compounds exhibited an AChE inhibition potential of the same order of magnitude as the positive control, galantamine (IC50 1.50 ± 0.10 ug/mL), however the semi-synthetic derivative 60 was considered inactive (IC50 > 300.00 ug/mL).
id UFU_b86ba142f5529a3aad8f0af6eac599f3
oai_identifier_str oai:repositorio.ufu.br:123456789/28461
network_acronym_str UFU
network_name_str Repositório Institucional da UFU
repository_id_str
spelling Análise estereoquímica dos alcaloides piperidínicos isolados de Senna spectabilis e avaliação do potencial anticolinesterásicoStereochemical analysis of piperidine alkaloids isolated from Senna spectabilis and evaluation of anticholinesterase potentialSenna spectabilisAlcaloides piperidínicosPiperidine alkaloidsEstereoquímicaStereochemistryCromatografiaChromatographyEspectrometria de massasMass spectrometryAnticolinesterásicosAnticholinesteraseCNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA ORGANICA::QUIMICA DOS PRODUTOS NATURAISNatural products have been used since ancient times as a way to cure or prevent human illness. Throughout history, compounds obtained from natural sources have aroused great interest due to the complexity of molecular arrangements associated with the three-dimensional dispositions of asymmetric carbons and your biological activities. Thus, for a long time, synthetic drugs were inspired by the structures of natural compounds, frequently chirals, which were produced in the form of racemates, ignoring the possible differences in biological activity that different stereoisomers could cause. Against this background, we have invested in the study of piperidine alkaloids present in Senna spectabilis, which have stereogenic centers and verified action on the central nervous system, as well as presenting various biological activities such as leishmanicide, antimalarial and anticholinesterase. In this sense, the present study describes the isolation process of chiral piperidine alkaloids from the ethanolic extract of Senna spectabilis flowers. This extract was submitted to liquid-liquid extraction with hexane and dichloromethane, being the second fraction with the highest concentration of alkaloids. This fraction was submitted to different chromatographic procedures, from which homologues 1 and 2, previously described in S. spectabilis, were isolated, as well as the two new homologous compounds, whose chromatographic and spectrometric analyzes indicate that they are diastereoisomers of 1 and 2. Then, the mixture containing 4 and 5 was subjected to an esterification reaction with acetyl chloride, obtaining compound 60. The natural and semi-synthetic compounds were evaluated in the acetylcholinesterase (AChE) inhibition test, where it was possible to observe that homologous alkaloids 1 (IC50 0.62 ± 0.01 ug/mL) and 2 (IC50 0.87 ± 0.12 ug/mL), with the same stereochemistry are more potent than the respective stereoisomers 4 (IC50 6.49 ± 0.23 ug/mL) and 5 (IC50 17.60 ± 1.90 ug/mL). These compounds exhibited an AChE inhibition potential of the same order of magnitude as the positive control, galantamine (IC50 1.50 ± 0.10 ug/mL), however the semi-synthetic derivative 60 was considered inactive (IC50 > 300.00 ug/mL).CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorFAPEMIG - Fundação de Amparo a Pesquisa do Estado de Minas GeraisRQMG - Rede Mineira de QuímicaTrabalho de Conclusão de Curso (Graduação)Os produtos naturais são utilizados desde a antiguidade como uma forma de cura ou prevenção dos males humanos. Ao longo da história, os compostos obtidos de fontes naturais têm despertado grande interesse devido à complexidade das arquiteturas moleculares relacionada às disposições tridimensionais dos carbonos assimétricos e atividades biológicas associadas. Assim, por muito tempo, fármacos sintéticos foram inspirados nas estruturas de compostos de origem natural e que frequentemente são quirais, os quais foram produzidos na forma de racematos, ignorando as possíveis diferenças de atividade biológica que os diferentes estereoisômeros poderiam proporcionar. Dentro deste contexto, temos investido no estudo dos alcaloides piperidínicos presentes em Senna spectabilis, que apresentam três centros estereogênicos e comprovada atuação sobre o sistema nervoso central, além de apresentarem diversas atividades biológicas como, leishmanicida, antimalárica e anticolinesterásica. Nesse sentido, o presente estudo descreve o processo de isolamento dos alcaloides piperidínicos quirais a partir do extrato etanólico das flores da Senna spectabilis. Esse extrato foi submetido à extração líquido-líquido com hexano e diclorometano, sendo a segunda fração aquela com maior concentração de alcaloides. Essa fração foi submetida a diferentes procedimentos cromatográficos, de onde foram isolados os homólogos 1 e 2, já descritos anteriormente em S. spectabilis, além dos dois novos compostos (4 e 5) também homólogos, cujas análises cromatográficas e espectrométricas realizadas indicam que são diastereoisômeros de 1 e 2. Em seguida, a mistura contendo 4 e 5 foi submetida a reação de esterificação com cloreto de acetila, de onde foi obtido o composto 60. Os compostos naturais e semissintéticos foram avaliados no ensaio de inibição da acetilcolinesterase (AChE) de onde foi possível observar que os alcaloides homólogos 1 (IC50 0,62 ± 0,01 ug/mL) e 2 (IC50 0,87 ± 0,12 ug/mL), de mesma estereoquímica são mais potentes que os respectivos estereoisômeros 4 (IC50 6,49 ± 0,23 ug/mL) e 5 (IC50 17,60 ± 1,90 ug/mL). Estes compostos apresentaram potencial de inibição da AChE da mesma ordem de grandeza que o controle positivo, galantamina (IC50 1,50 ± 0,10 ug/mL), no entanto o derivado semissintético 60 foi considerado inativo (IC50 > 300,00 ug/mL).Universidade Federal de UberlândiaBrasilQuímica IndustrialFreitas, Thamires Rodrigueshttp://lattes.cnpq.br/2247698910822909Pivatto, Marcoshttp://lattes.cnpq.br/7781239794922114Sousa, Raquel Maria Ferreira dehttp://lattes.cnpq.br/6064800347452834Takahashi, Leticia Masakohttp://lattes.cnpq.br/7624474336415464Cunha, Luís Carlos Scalonhttp://lattes.cnpq.br/4091661421232953Novais, Raul Marques2020-01-22T16:08:54Z2020-01-22T16:08:54Z2019-12-20info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/bachelorThesisapplication/pdfNOVAIS, Raul Marques. Análise estereoquímica dos alcaloides piperidínicos isolados de Senna spectabilis e avaliação do potencial anticolinesterásico. 2019. 81 f. Trabalho de Conclusão de Curso (Graduação em Química Industrial) – Universidade Federal de Uberlândia, Uberlândia, 2020.https://repositorio.ufu.br/handle/123456789/28461porhttp://creativecommons.org/publicdomain/zero/1.0/info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFUinstname:Universidade Federal de Uberlândia (UFU)instacron:UFU2020-01-23T06:12:30Zoai:repositorio.ufu.br:123456789/28461Repositório InstitucionalONGhttp://repositorio.ufu.br/oai/requestdiinf@dirbi.ufu.bropendoar:2020-01-23T06:12:30Repositório Institucional da UFU - Universidade Federal de Uberlândia (UFU)false
dc.title.none.fl_str_mv Análise estereoquímica dos alcaloides piperidínicos isolados de Senna spectabilis e avaliação do potencial anticolinesterásico
Stereochemical analysis of piperidine alkaloids isolated from Senna spectabilis and evaluation of anticholinesterase potential
title Análise estereoquímica dos alcaloides piperidínicos isolados de Senna spectabilis e avaliação do potencial anticolinesterásico
spellingShingle Análise estereoquímica dos alcaloides piperidínicos isolados de Senna spectabilis e avaliação do potencial anticolinesterásico
Novais, Raul Marques
Senna spectabilis
Alcaloides piperidínicos
Piperidine alkaloids
Estereoquímica
Stereochemistry
Cromatografia
Chromatography
Espectrometria de massas
Mass spectrometry
Anticolinesterásicos
Anticholinesterase
CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA ORGANICA::QUIMICA DOS PRODUTOS NATURAIS
title_short Análise estereoquímica dos alcaloides piperidínicos isolados de Senna spectabilis e avaliação do potencial anticolinesterásico
title_full Análise estereoquímica dos alcaloides piperidínicos isolados de Senna spectabilis e avaliação do potencial anticolinesterásico
title_fullStr Análise estereoquímica dos alcaloides piperidínicos isolados de Senna spectabilis e avaliação do potencial anticolinesterásico
title_full_unstemmed Análise estereoquímica dos alcaloides piperidínicos isolados de Senna spectabilis e avaliação do potencial anticolinesterásico
title_sort Análise estereoquímica dos alcaloides piperidínicos isolados de Senna spectabilis e avaliação do potencial anticolinesterásico
author Novais, Raul Marques
author_facet Novais, Raul Marques
author_role author
dc.contributor.none.fl_str_mv Freitas, Thamires Rodrigues
http://lattes.cnpq.br/2247698910822909
Pivatto, Marcos
http://lattes.cnpq.br/7781239794922114
Sousa, Raquel Maria Ferreira de
http://lattes.cnpq.br/6064800347452834
Takahashi, Leticia Masako
http://lattes.cnpq.br/7624474336415464
Cunha, Luís Carlos Scalon
http://lattes.cnpq.br/4091661421232953
dc.contributor.author.fl_str_mv Novais, Raul Marques
dc.subject.por.fl_str_mv Senna spectabilis
Alcaloides piperidínicos
Piperidine alkaloids
Estereoquímica
Stereochemistry
Cromatografia
Chromatography
Espectrometria de massas
Mass spectrometry
Anticolinesterásicos
Anticholinesterase
CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA ORGANICA::QUIMICA DOS PRODUTOS NATURAIS
topic Senna spectabilis
Alcaloides piperidínicos
Piperidine alkaloids
Estereoquímica
Stereochemistry
Cromatografia
Chromatography
Espectrometria de massas
Mass spectrometry
Anticolinesterásicos
Anticholinesterase
CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA ORGANICA::QUIMICA DOS PRODUTOS NATURAIS
description Natural products have been used since ancient times as a way to cure or prevent human illness. Throughout history, compounds obtained from natural sources have aroused great interest due to the complexity of molecular arrangements associated with the three-dimensional dispositions of asymmetric carbons and your biological activities. Thus, for a long time, synthetic drugs were inspired by the structures of natural compounds, frequently chirals, which were produced in the form of racemates, ignoring the possible differences in biological activity that different stereoisomers could cause. Against this background, we have invested in the study of piperidine alkaloids present in Senna spectabilis, which have stereogenic centers and verified action on the central nervous system, as well as presenting various biological activities such as leishmanicide, antimalarial and anticholinesterase. In this sense, the present study describes the isolation process of chiral piperidine alkaloids from the ethanolic extract of Senna spectabilis flowers. This extract was submitted to liquid-liquid extraction with hexane and dichloromethane, being the second fraction with the highest concentration of alkaloids. This fraction was submitted to different chromatographic procedures, from which homologues 1 and 2, previously described in S. spectabilis, were isolated, as well as the two new homologous compounds, whose chromatographic and spectrometric analyzes indicate that they are diastereoisomers of 1 and 2. Then, the mixture containing 4 and 5 was subjected to an esterification reaction with acetyl chloride, obtaining compound 60. The natural and semi-synthetic compounds were evaluated in the acetylcholinesterase (AChE) inhibition test, where it was possible to observe that homologous alkaloids 1 (IC50 0.62 ± 0.01 ug/mL) and 2 (IC50 0.87 ± 0.12 ug/mL), with the same stereochemistry are more potent than the respective stereoisomers 4 (IC50 6.49 ± 0.23 ug/mL) and 5 (IC50 17.60 ± 1.90 ug/mL). These compounds exhibited an AChE inhibition potential of the same order of magnitude as the positive control, galantamine (IC50 1.50 ± 0.10 ug/mL), however the semi-synthetic derivative 60 was considered inactive (IC50 > 300.00 ug/mL).
publishDate 2019
dc.date.none.fl_str_mv 2019-12-20
2020-01-22T16:08:54Z
2020-01-22T16:08:54Z
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 NOVAIS, Raul Marques. Análise estereoquímica dos alcaloides piperidínicos isolados de Senna spectabilis e avaliação do potencial anticolinesterásico. 2019. 81 f. Trabalho de Conclusão de Curso (Graduação em Química Industrial) – Universidade Federal de Uberlândia, Uberlândia, 2020.
https://repositorio.ufu.br/handle/123456789/28461
identifier_str_mv NOVAIS, Raul Marques. Análise estereoquímica dos alcaloides piperidínicos isolados de Senna spectabilis e avaliação do potencial anticolinesterásico. 2019. 81 f. Trabalho de Conclusão de Curso (Graduação em Química Industrial) – Universidade Federal de Uberlândia, Uberlândia, 2020.
url https://repositorio.ufu.br/handle/123456789/28461
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv http://creativecommons.org/publicdomain/zero/1.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/publicdomain/zero/1.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade Federal de Uberlândia
Brasil
Química Industrial
publisher.none.fl_str_mv Universidade Federal de Uberlândia
Brasil
Química Industrial
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFU
instname:Universidade Federal de Uberlândia (UFU)
instacron:UFU
instname_str Universidade Federal de Uberlândia (UFU)
instacron_str UFU
institution UFU
reponame_str Repositório Institucional da UFU
collection Repositório Institucional da UFU
repository.name.fl_str_mv Repositório Institucional da UFU - Universidade Federal de Uberlândia (UFU)
repository.mail.fl_str_mv diinf@dirbi.ufu.br
_version_ 1813711302507364352