Novel chalcones derivatives with potential antineoplastic activity investigated by docking and molecular dynamics simulations
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Digital do Instituto Evandro Chagas (Patuá) |
Texto Completo: | https://patua.iec.gov.br/handle/iec/4200 |
Resumo: | Glioblastoma is an aggressive primary tumor of the central nervous system (CNS). Is the most aggressive among infiltrative gliomas arising from the CNS. This tumor has low patient survival rate and several studies aiming at developing new drugs have increased. Patients with this cancer type face significant morbidity and mortality. This study evaluated the antineoplastic activity of synthetic chalcones (3a-3f) using in vitro glioblastoma models and molecular modeling. Cytotoxicity assay showed that Astrocitoma Hospital Ofir Loyola No 1 (AHOL1) and Uppsala 87 neoplastic glioblastoma lines (U87) cellular viability were significantly reduced compared to Healthy human fibroblasts cell lines (AN27) when exposed to chalcones. Interaction with the serine amino acid was present in the most promising and the reference binder docking, suggesting its importance inhibiting cell growth. Comparative analysis between the reference ligands and the molecules showed that the amino acid LYS352 present in all fittings, suggesting that this is the main amino acid for interaction with tubulin and are consistent with those in cytotoxicity assay, suggesting antineoplastic potential in glioblastoma. Long trajectory molecular dynamics studies were also carried out in order to investigate stability and conformations amongst the chalcones bound tubulin as well, in comparison to doxorubicin (here used as control), however future studies are needed to further assess the mechanism of inhibition of chalcones used in this investigation. |
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M. Neto, Raimundo de ASantos, Cleydson B. RHenriques, Shayanne V. CMachado, Letícia de OCruz, Jorddy NevesSilva, Carlos H. T. de P. daFederico, Leonardo BOliveira, Edivaldo Herculano Corrêa deSouza, Michel P. C. deSilva, Patrícia N. B. daTaft, Carlton AFerreira, Irlon MGomes, Madson R. F2020-11-16T17:38:31Z2020-11-16T17:38:31Z2022M. NETO, Raimundo de A. et al. Novel chalcones derivatives with potential antineoplastic activity investigated by docking and molecular dynamics simulations. Journal of Biomolecular Structure and Dynamics, v. 40, n. 5. p. 2204-2216, 20220739-1102https://patua.iec.gov.br/handle/iec/420010.1080/07391102.2020.1839562Glioblastoma is an aggressive primary tumor of the central nervous system (CNS). Is the most aggressive among infiltrative gliomas arising from the CNS. This tumor has low patient survival rate and several studies aiming at developing new drugs have increased. Patients with this cancer type face significant morbidity and mortality. This study evaluated the antineoplastic activity of synthetic chalcones (3a-3f) using in vitro glioblastoma models and molecular modeling. Cytotoxicity assay showed that Astrocitoma Hospital Ofir Loyola No 1 (AHOL1) and Uppsala 87 neoplastic glioblastoma lines (U87) cellular viability were significantly reduced compared to Healthy human fibroblasts cell lines (AN27) when exposed to chalcones. Interaction with the serine amino acid was present in the most promising and the reference binder docking, suggesting its importance inhibiting cell growth. Comparative analysis between the reference ligands and the molecules showed that the amino acid LYS352 present in all fittings, suggesting that this is the main amino acid for interaction with tubulin and are consistent with those in cytotoxicity assay, suggesting antineoplastic potential in glioblastoma. Long trajectory molecular dynamics studies were also carried out in order to investigate stability and conformations amongst the chalcones bound tubulin as well, in comparison to doxorubicin (here used as control), however future studies are needed to further assess the mechanism of inhibition of chalcones used in this investigation.Universidade Federal do Amapá. Departamento de Ciências Biológicas e da Saúde. Macapá, AP, Brasil.Universidade Federal do Amapá. Departamento de Ciências Biológicas e da Saúde. Macapá, AP, Brasil.Universidade Federal do Amapá. Departamento de Ciências Biológicas e da Saúde. Macapá, AP, Brasil.Universidade Federal do Amapá. Departamento de Ciências Biológicas e da Saúde. Macapá, AP, Brasil.Universidade de São Paulo. Faculdade de Ciências Farmacêuticas de Ribeirão Preto. Ribeirão Preto, SP, Brasil.Universidade de São Paulo. Faculdade de Ciências Farmacêuticas de Ribeirão Preto. Ribeirão Preto, SP, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Universidade Federal do Amapá. Colegiado de Química. Macapá, AP, Brasil.Centro Brasileiro de Pesquisas Físicas. Urca, RJ, Brasil.Universidade Federal do Amapá. Colegiado de Química. Macapá, AP, Brasil.Universidade Federal do Amapá. Departamento de Ciências Biológicas e da Saúde. Macapá, AP, Brasil.engTaylor & FrancisNovel chalcones derivatives with potential antineoplastic activity investigated by docking and molecular dynamics simulationsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleSistema Nervoso CentralNeoplasias do Sistema Nervoso CentralGlioblastomaChalconasSimulação de Acoplamento MolecularSimulação de Dinâmica Molecularinfo:eu-repo/semantics/embargoedAccessreponame:Repositório Digital do Instituto Evandro Chagas (Patuá)instname:Instituto Evandro Chagas (IEC)instacron:IECORIGINALNovel chalcones derivatives with potential antineoplastic activity investigated by docking and molecular dynamics simulations.pdfNovel chalcones derivatives with potential antineoplastic activity investigated by docking and molecular dynamics simulations.pdfapplication/pdf551083https://patua.iec.gov.br/bitstreams/dd8e30fa-2f2f-4f36-9472-7c183d74ed27/downloadc9a9c128e29cac82a5d7fdf3f4e6da73MD51TEXTNovel chalcones derivatives with potential antineoplastic activity investigated by docking and molecular dynamics simulations.pdf.txtNovel chalcones derivatives with potential antineoplastic activity investigated by docking and molecular dynamics simulations.pdf.txtExtracted texttext/plain2https://patua.iec.gov.br/bitstreams/1f24c195-a125-46a8-bf66-b00e47162752/downloade1c06d85ae7b8b032bef47e42e4c08f9MD55THUMBNAILNovel chalcones derivatives with potential antineoplastic activity investigated by docking and molecular dynamics simulations.pdf.jpgNovel chalcones derivatives with potential antineoplastic activity investigated by docking and molecular dynamics simulations.pdf.jpgGenerated Thumbnailimage/jpeg3095https://patua.iec.gov.br/bitstreams/ea745466-80bc-4ff2-8c19-c7ba9ba2e361/download71859d578212107f7f8c49a4ce09d9eeMD56LICENSElicense.txtlicense.txttext/plain; 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dc.title.pt_BR.fl_str_mv |
Novel chalcones derivatives with potential antineoplastic activity investigated by docking and molecular dynamics simulations |
title |
Novel chalcones derivatives with potential antineoplastic activity investigated by docking and molecular dynamics simulations |
spellingShingle |
Novel chalcones derivatives with potential antineoplastic activity investigated by docking and molecular dynamics simulations M. Neto, Raimundo de A Sistema Nervoso Central Neoplasias do Sistema Nervoso Central Glioblastoma Chalconas Simulação de Acoplamento Molecular Simulação de Dinâmica Molecular |
title_short |
Novel chalcones derivatives with potential antineoplastic activity investigated by docking and molecular dynamics simulations |
title_full |
Novel chalcones derivatives with potential antineoplastic activity investigated by docking and molecular dynamics simulations |
title_fullStr |
Novel chalcones derivatives with potential antineoplastic activity investigated by docking and molecular dynamics simulations |
title_full_unstemmed |
Novel chalcones derivatives with potential antineoplastic activity investigated by docking and molecular dynamics simulations |
title_sort |
Novel chalcones derivatives with potential antineoplastic activity investigated by docking and molecular dynamics simulations |
author |
M. Neto, Raimundo de A |
author_facet |
M. Neto, Raimundo de A Santos, Cleydson B. R Henriques, Shayanne V. C Machado, Letícia de O Cruz, Jorddy Neves Silva, Carlos H. T. de P. da Federico, Leonardo B Oliveira, Edivaldo Herculano Corrêa de Souza, Michel P. C. de Silva, Patrícia N. B. da Taft, Carlton A Ferreira, Irlon M Gomes, Madson R. F |
author_role |
author |
author2 |
Santos, Cleydson B. R Henriques, Shayanne V. C Machado, Letícia de O Cruz, Jorddy Neves Silva, Carlos H. T. de P. da Federico, Leonardo B Oliveira, Edivaldo Herculano Corrêa de Souza, Michel P. C. de Silva, Patrícia N. B. da Taft, Carlton A Ferreira, Irlon M Gomes, Madson R. F |
author2_role |
author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
M. Neto, Raimundo de A Santos, Cleydson B. R Henriques, Shayanne V. C Machado, Letícia de O Cruz, Jorddy Neves Silva, Carlos H. T. de P. da Federico, Leonardo B Oliveira, Edivaldo Herculano Corrêa de Souza, Michel P. C. de Silva, Patrícia N. B. da Taft, Carlton A Ferreira, Irlon M Gomes, Madson R. F |
dc.subject.decsPrimary.pt_BR.fl_str_mv |
Sistema Nervoso Central Neoplasias do Sistema Nervoso Central Glioblastoma Chalconas Simulação de Acoplamento Molecular Simulação de Dinâmica Molecular |
topic |
Sistema Nervoso Central Neoplasias do Sistema Nervoso Central Glioblastoma Chalconas Simulação de Acoplamento Molecular Simulação de Dinâmica Molecular |
description |
Glioblastoma is an aggressive primary tumor of the central nervous system (CNS). Is the most aggressive among infiltrative gliomas arising from the CNS. This tumor has low patient survival rate and several studies aiming at developing new drugs have increased. Patients with this cancer type face significant morbidity and mortality. This study evaluated the antineoplastic activity of synthetic chalcones (3a-3f) using in vitro glioblastoma models and molecular modeling. Cytotoxicity assay showed that Astrocitoma Hospital Ofir Loyola No 1 (AHOL1) and Uppsala 87 neoplastic glioblastoma lines (U87) cellular viability were significantly reduced compared to Healthy human fibroblasts cell lines (AN27) when exposed to chalcones. Interaction with the serine amino acid was present in the most promising and the reference binder docking, suggesting its importance inhibiting cell growth. Comparative analysis between the reference ligands and the molecules showed that the amino acid LYS352 present in all fittings, suggesting that this is the main amino acid for interaction with tubulin and are consistent with those in cytotoxicity assay, suggesting antineoplastic potential in glioblastoma. Long trajectory molecular dynamics studies were also carried out in order to investigate stability and conformations amongst the chalcones bound tubulin as well, in comparison to doxorubicin (here used as control), however future studies are needed to further assess the mechanism of inhibition of chalcones used in this investigation. |
publishDate |
2020 |
dc.date.accessioned.fl_str_mv |
2020-11-16T17:38:31Z |
dc.date.available.fl_str_mv |
2020-11-16T17:38:31Z |
dc.date.issued.fl_str_mv |
2022 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
M. NETO, Raimundo de A. et al. Novel chalcones derivatives with potential antineoplastic activity investigated by docking and molecular dynamics simulations. Journal of Biomolecular Structure and Dynamics, v. 40, n. 5. p. 2204-2216, 2022 |
dc.identifier.uri.fl_str_mv |
https://patua.iec.gov.br/handle/iec/4200 |
dc.identifier.issn.-.fl_str_mv |
0739-1102 |
dc.identifier.doi.-.fl_str_mv |
10.1080/07391102.2020.1839562 |
identifier_str_mv |
M. NETO, Raimundo de A. et al. Novel chalcones derivatives with potential antineoplastic activity investigated by docking and molecular dynamics simulations. Journal of Biomolecular Structure and Dynamics, v. 40, n. 5. p. 2204-2216, 2022 0739-1102 10.1080/07391102.2020.1839562 |
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https://patua.iec.gov.br/handle/iec/4200 |
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eng |
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eng |
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dc.publisher.none.fl_str_mv |
Taylor & Francis |
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Taylor & Francis |
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