Alcaloides β-carbolínicos: interação com DNA (Calf thymus), proteína de soro bovino (BSA), correlação com atividade biológica e Docking molecular

Detalhes bibliográficos
Autor(a) principal: Pereira, Karlly Thayanny de Oliveira
Data de Publicação: 2018
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da Universidade Federal de Alagoas (UFAL)
Texto Completo: http://www.repositorio.ufal.br/handle/riufal/3717
Resumo: The alkaloids derived from the β-carbolines have several biological activity, being their greater prominence attributed the anticancer activities. This property, therefore, has aroused the interest of the synthetic chemists in the search of new prototypes to the anticancer drugs. However, the design of more promising drugs requires information that can be obtained from the study of the interaction of these small molecules with DNA and BSA protein. This is because DNA is the main target of several drugs, including anticancer drugs, while BSA is the multi-drug Carrier protein, which influences their effectiveness. For this reason, the study of the interaction of small molecules with these macromolecules has been advancing in recent decades. In this context, the objective of the present study was to evaluate the interaction of β-carbolinic alkaloids with ctDNA (Calf thymus) and also with the bovine serum albumin (BSA) protein, by means of absorption spectroscopy techniques in UV-visible and molecular fluorescence. The results showed that there was interaction of the compounds derived from β-carbolinic alkaloids with the two macromolecules evaluated, ctDNA and BSA, resulting in the formation of nonfluorescent supramolecular complexes through the static quenching mechanism. In the study with ctDNA, it was observed that the interaction of the compounds with the macromolecule was significant, with values of the binding constants, Kb, ranging from 2.45×104 to 1.18×106 L mol-1, reaction performed in the ratio of 1:1 (compound: ctDNA). The highest Kb value was exhibited by compound 9c, which has an N,N-dimethylaniline group at the C1 position in the β-carboline ring, whereas for compound 9e, having the substituent at C1 o-chlorophenyl, showed the lowest value of Kb. The main mode of interaction occurs preferentially via intercalation, which was established by potassium iodide (KI) and ethidium bromide (EB) assays. From the study of the analytical correlation between the values of Kb vs IG50, it was possible to observe that the intercalation mode, for some compounds, is the main mechanism of anticancer action of the same. Correlation was therefore found for colon (HT-29) strains, for compounds 9e, 10b, 9c; and kidney (786-0) for compounds 9e, 17 and 9c. For the study with the BSA protein, the Kb values ranged from 3.2×104 to 4.1×106 L mol-1, the highest value corresponding to 9e, shown a good affinity with the protein and, with a stoichiometric ratio of 1:1. Finally, it was observed by molecular docking that the compounds studied have good affinity with a hydrophobic cavity contained in the site I of the protein, located in subdomain IIA where the tryptophan (Trp213) residue is found. Thus, it is possible to state that the bioactive compounds evaluated, derived from β-carbolines, have an affinity with both DNA and BSA protein.
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spelling Alcaloides β-carbolínicos: interação com DNA (Calf thymus), proteína de soro bovino (BSA), correlação com atividade biológica e Docking molecularβ-carbolinal alkaloids: interaction with DNA (Calf thymus), bovine serum protein (BSA), correlation with biological activity and molecular DockingInteração de moléculasAlcaloides β-carbolinasEspectrocopiaCorrelação bioanalíticaDocking molecularInteractionβ-carbolinesctDNABSAEspectroscopio techniquesBioanalytical correlationMolecular DockingCNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA ANALITICAThe alkaloids derived from the β-carbolines have several biological activity, being their greater prominence attributed the anticancer activities. This property, therefore, has aroused the interest of the synthetic chemists in the search of new prototypes to the anticancer drugs. However, the design of more promising drugs requires information that can be obtained from the study of the interaction of these small molecules with DNA and BSA protein. This is because DNA is the main target of several drugs, including anticancer drugs, while BSA is the multi-drug Carrier protein, which influences their effectiveness. For this reason, the study of the interaction of small molecules with these macromolecules has been advancing in recent decades. In this context, the objective of the present study was to evaluate the interaction of β-carbolinic alkaloids with ctDNA (Calf thymus) and also with the bovine serum albumin (BSA) protein, by means of absorption spectroscopy techniques in UV-visible and molecular fluorescence. The results showed that there was interaction of the compounds derived from β-carbolinic alkaloids with the two macromolecules evaluated, ctDNA and BSA, resulting in the formation of nonfluorescent supramolecular complexes through the static quenching mechanism. In the study with ctDNA, it was observed that the interaction of the compounds with the macromolecule was significant, with values of the binding constants, Kb, ranging from 2.45×104 to 1.18×106 L mol-1, reaction performed in the ratio of 1:1 (compound: ctDNA). The highest Kb value was exhibited by compound 9c, which has an N,N-dimethylaniline group at the C1 position in the β-carboline ring, whereas for compound 9e, having the substituent at C1 o-chlorophenyl, showed the lowest value of Kb. The main mode of interaction occurs preferentially via intercalation, which was established by potassium iodide (KI) and ethidium bromide (EB) assays. From the study of the analytical correlation between the values of Kb vs IG50, it was possible to observe that the intercalation mode, for some compounds, is the main mechanism of anticancer action of the same. Correlation was therefore found for colon (HT-29) strains, for compounds 9e, 10b, 9c; and kidney (786-0) for compounds 9e, 17 and 9c. For the study with the BSA protein, the Kb values ranged from 3.2×104 to 4.1×106 L mol-1, the highest value corresponding to 9e, shown a good affinity with the protein and, with a stoichiometric ratio of 1:1. Finally, it was observed by molecular docking that the compounds studied have good affinity with a hydrophobic cavity contained in the site I of the protein, located in subdomain IIA where the tryptophan (Trp213) residue is found. Thus, it is possible to state that the bioactive compounds evaluated, derived from β-carbolines, have an affinity with both DNA and BSA protein.FAPEAL - Fundação de Amparo à Pesquisa do Estado de AlagoasOs alcaloides derivados das β-carbolinas possuem diversas atividades biológicas, sendo seu maior destaque atribuído às atividades anticâncers. Esta propriedade, portanto, tem despertado o interesse dos químicos sintéticos na busca de novos protótipos a fármacos anticancerígenos. Porém, o design de medicamentos mais promissores necessita de informações que podem ser obtidas a partir do estudo da interação destas pequenas moléculas com o DNA e a proteína BSA. Isso porque o DNA é o principal alvo de diversos fármacos, incluindo os anticancerígenos, enquanto que a BSA é a proteína carreadora de vários medicamentos o que influencia na eficácia dos mesmos. Por esse motivo, o estudo da interação de pequenas moléculas com estas macromoléculas vem avançando nas últimas décadas. Neste contexto, o objetivo do presente trabalho foi avaliar a interação de alcaloides β-carbolínicos com o ctDNA (Calf thymus) e, também, com a proteína albumina de soro bovino (BSA), por meio das técnicas de espectroscopia de absorção no UV-Visível e de fluorescência molecular. Os resultados mostraram que houve interação dos compostos derivados de alcaloides β-carbolínicos com as duas macromoléculas avaliadas, ctDNA e BSA, resultando em formação de complexos supramoleculares não fluorescentes através do mecanismo de quenching estático. No estudo com o ctDNA, pode-se observar que a interação dos compostos com a macromolécula foi significativa, com valores das constantes de ligação, Kb, variando na faixa de 2,45×104 a 1,18×106 L mol-1, sendo a reação efetuada na proporção de 1:1 (composto:ctDNA). O maior valor de Kb foi exibido pelo composto 9c, o qual possui um grupo N,N-dimetilanilina na posição C1 no anel β-carbolina, enquanto que para o composto 9e, possuindo o substituinte em C1 o-cloro fenil, apresentou o menor valor de Kb. O principal modo da interação ocorre preferencialmente via intercalação, o qual foi estabelecido por meio dos ensaios com o iodeto de potássio (KI) e brometo de etídio (BE). A partir do estudo da correlação analítica entre os valores de Kb vs IG50, foi possível observar que o modo intercalativo, para alguns compostos, é o principal mecanismo de ação anticâncer do mesmo. A correlação foi, portanto, encontrada para linhagens de cólon (HT-29), para os compostos 9e, 10b, 9c; e de rim (786-0) para os compostos 9e, 17 e 9c. Para o estudo com a proteína BSA, os valores de Kb variaram de 3,2×104 a 4,1×106 L mol- 1, sendo o maior valor correspondente ao composto 9e, demonstrando uma boa afinidade com a proteína e, apresentando relação estequiométrica de 1:1. Por fim, foi visualizado por meio do docking molecular que os compostos estudados possuem boa afinidade com a cavidade hidrofóbica contida no sítio I da proteína, localizado no subdomínio IIA onde é encontrado o resíduo de triptofano (Trp213). Dessa forma, é possível afirmar que os compostos bioativos avaliados, derivados das β-carbolinas, possuem afinidade tanto com o DNA, quanto com a proteína BSA.Universidade Federal de AlagoasBrasilPrograma de Pós-Graduação em Química e BiotecnologiaUFALFigueiredo, Isis Martinshttp://lattes.cnpq.br/2526310794411188Santos, Josué Carinhanha Caldashttp://lattes.cnpq.br/3735618604163061Müller, Camilla Djenne Buarquehttp://lattes.cnpq.br/4866073046756466Aquino, Thiago Mendonça dehttp://lattes.cnpq.br/3395195195361558Pereira, Karlly Thayanny de Oliveira2019-01-09T16:05:55Z2019-01-092019-01-09T16:05:55Z2018-09-05info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfPEREIRA, Karlly Thayanny de Oliveira. Alcaloides β-carbolínicos: interação com DNA (Calf thymus), proteína de soro bovino (BSA), correlação com atividade biológica e Docking molecular. 2018. 88 f. Dissertação (Mestrado em Química e Biotecnologia) – Instituto de Química e Biotecnologia, Programa de Pós-Graduação em Química e Biotecnologia, Universidade Federal de Alagoas, Maceió, 2019.http://www.repositorio.ufal.br/handle/riufal/3717porinfo:eu-repo/semantics/embargoedAccessreponame:Repositório Institucional da Universidade Federal de Alagoas (UFAL)instname:Universidade Federal de Alagoas (UFAL)instacron:UFAL2019-01-09T16:07:52Zoai:www.repositorio.ufal.br:riufal/3717Repositório InstitucionalPUBhttp://www.repositorio.ufal.br/oai/requestri@sibi.ufal.bropendoar:2019-01-09T16:07:52Repositório Institucional da Universidade Federal de Alagoas (UFAL) - Universidade Federal de Alagoas (UFAL)false
dc.title.none.fl_str_mv Alcaloides β-carbolínicos: interação com DNA (Calf thymus), proteína de soro bovino (BSA), correlação com atividade biológica e Docking molecular
β-carbolinal alkaloids: interaction with DNA (Calf thymus), bovine serum protein (BSA), correlation with biological activity and molecular Docking
title Alcaloides β-carbolínicos: interação com DNA (Calf thymus), proteína de soro bovino (BSA), correlação com atividade biológica e Docking molecular
spellingShingle Alcaloides β-carbolínicos: interação com DNA (Calf thymus), proteína de soro bovino (BSA), correlação com atividade biológica e Docking molecular
Pereira, Karlly Thayanny de Oliveira
Interação de moléculas
Alcaloides β-carbolinas
Espectrocopia
Correlação bioanalítica
Docking molecular
Interaction
β-carbolines
ctDNA
BSA
Espectroscopio techniques
Bioanalytical correlation
Molecular Docking
CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA ANALITICA
title_short Alcaloides β-carbolínicos: interação com DNA (Calf thymus), proteína de soro bovino (BSA), correlação com atividade biológica e Docking molecular
title_full Alcaloides β-carbolínicos: interação com DNA (Calf thymus), proteína de soro bovino (BSA), correlação com atividade biológica e Docking molecular
title_fullStr Alcaloides β-carbolínicos: interação com DNA (Calf thymus), proteína de soro bovino (BSA), correlação com atividade biológica e Docking molecular
title_full_unstemmed Alcaloides β-carbolínicos: interação com DNA (Calf thymus), proteína de soro bovino (BSA), correlação com atividade biológica e Docking molecular
title_sort Alcaloides β-carbolínicos: interação com DNA (Calf thymus), proteína de soro bovino (BSA), correlação com atividade biológica e Docking molecular
author Pereira, Karlly Thayanny de Oliveira
author_facet Pereira, Karlly Thayanny de Oliveira
author_role author
dc.contributor.none.fl_str_mv Figueiredo, Isis Martins
http://lattes.cnpq.br/2526310794411188
Santos, Josué Carinhanha Caldas
http://lattes.cnpq.br/3735618604163061
Müller, Camilla Djenne Buarque
http://lattes.cnpq.br/4866073046756466
Aquino, Thiago Mendonça de
http://lattes.cnpq.br/3395195195361558
dc.contributor.author.fl_str_mv Pereira, Karlly Thayanny de Oliveira
dc.subject.por.fl_str_mv Interação de moléculas
Alcaloides β-carbolinas
Espectrocopia
Correlação bioanalítica
Docking molecular
Interaction
β-carbolines
ctDNA
BSA
Espectroscopio techniques
Bioanalytical correlation
Molecular Docking
CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA ANALITICA
topic Interação de moléculas
Alcaloides β-carbolinas
Espectrocopia
Correlação bioanalítica
Docking molecular
Interaction
β-carbolines
ctDNA
BSA
Espectroscopio techniques
Bioanalytical correlation
Molecular Docking
CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA ANALITICA
description The alkaloids derived from the β-carbolines have several biological activity, being their greater prominence attributed the anticancer activities. This property, therefore, has aroused the interest of the synthetic chemists in the search of new prototypes to the anticancer drugs. However, the design of more promising drugs requires information that can be obtained from the study of the interaction of these small molecules with DNA and BSA protein. This is because DNA is the main target of several drugs, including anticancer drugs, while BSA is the multi-drug Carrier protein, which influences their effectiveness. For this reason, the study of the interaction of small molecules with these macromolecules has been advancing in recent decades. In this context, the objective of the present study was to evaluate the interaction of β-carbolinic alkaloids with ctDNA (Calf thymus) and also with the bovine serum albumin (BSA) protein, by means of absorption spectroscopy techniques in UV-visible and molecular fluorescence. The results showed that there was interaction of the compounds derived from β-carbolinic alkaloids with the two macromolecules evaluated, ctDNA and BSA, resulting in the formation of nonfluorescent supramolecular complexes through the static quenching mechanism. In the study with ctDNA, it was observed that the interaction of the compounds with the macromolecule was significant, with values of the binding constants, Kb, ranging from 2.45×104 to 1.18×106 L mol-1, reaction performed in the ratio of 1:1 (compound: ctDNA). The highest Kb value was exhibited by compound 9c, which has an N,N-dimethylaniline group at the C1 position in the β-carboline ring, whereas for compound 9e, having the substituent at C1 o-chlorophenyl, showed the lowest value of Kb. The main mode of interaction occurs preferentially via intercalation, which was established by potassium iodide (KI) and ethidium bromide (EB) assays. From the study of the analytical correlation between the values of Kb vs IG50, it was possible to observe that the intercalation mode, for some compounds, is the main mechanism of anticancer action of the same. Correlation was therefore found for colon (HT-29) strains, for compounds 9e, 10b, 9c; and kidney (786-0) for compounds 9e, 17 and 9c. For the study with the BSA protein, the Kb values ranged from 3.2×104 to 4.1×106 L mol-1, the highest value corresponding to 9e, shown a good affinity with the protein and, with a stoichiometric ratio of 1:1. Finally, it was observed by molecular docking that the compounds studied have good affinity with a hydrophobic cavity contained in the site I of the protein, located in subdomain IIA where the tryptophan (Trp213) residue is found. Thus, it is possible to state that the bioactive compounds evaluated, derived from β-carbolines, have an affinity with both DNA and BSA protein.
publishDate 2018
dc.date.none.fl_str_mv 2018-09-05
2019-01-09T16:05:55Z
2019-01-09
2019-01-09T16:05:55Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv PEREIRA, Karlly Thayanny de Oliveira. Alcaloides β-carbolínicos: interação com DNA (Calf thymus), proteína de soro bovino (BSA), correlação com atividade biológica e Docking molecular. 2018. 88 f. Dissertação (Mestrado em Química e Biotecnologia) – Instituto de Química e Biotecnologia, Programa de Pós-Graduação em Química e Biotecnologia, Universidade Federal de Alagoas, Maceió, 2019.
http://www.repositorio.ufal.br/handle/riufal/3717
identifier_str_mv PEREIRA, Karlly Thayanny de Oliveira. Alcaloides β-carbolínicos: interação com DNA (Calf thymus), proteína de soro bovino (BSA), correlação com atividade biológica e Docking molecular. 2018. 88 f. Dissertação (Mestrado em Química e Biotecnologia) – Instituto de Química e Biotecnologia, Programa de Pós-Graduação em Química e Biotecnologia, Universidade Federal de Alagoas, Maceió, 2019.
url http://www.repositorio.ufal.br/handle/riufal/3717
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/embargoedAccess
eu_rights_str_mv embargoedAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade Federal de Alagoas
Brasil
Programa de Pós-Graduação em Química e Biotecnologia
UFAL
publisher.none.fl_str_mv Universidade Federal de Alagoas
Brasil
Programa de Pós-Graduação em Química e Biotecnologia
UFAL
dc.source.none.fl_str_mv reponame:Repositório Institucional da Universidade Federal de Alagoas (UFAL)
instname:Universidade Federal de Alagoas (UFAL)
instacron:UFAL
instname_str Universidade Federal de Alagoas (UFAL)
instacron_str UFAL
institution UFAL
reponame_str Repositório Institucional da Universidade Federal de Alagoas (UFAL)
collection Repositório Institucional da Universidade Federal de Alagoas (UFAL)
repository.name.fl_str_mv Repositório Institucional da Universidade Federal de Alagoas (UFAL) - Universidade Federal de Alagoas (UFAL)
repository.mail.fl_str_mv ri@sibi.ufal.br
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