Novel chalcones derivatives with potential antineoplastic activity investigated by docking and molecular dynamics simulations

Detalhes bibliográficos
Autor(a) principal: M. Neto, Raimundo de A
Data de Publicação: 2020
Outros Autores: 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
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.
id IEC-2_1fa87833a6e4f6a89e6dceb474d5b86a
oai_identifier_str oai:patua.iec.gov.br:iec/4200
network_acronym_str IEC-2
network_name_str Repositório Digital do Instituto Evandro Chagas (Patuá)
repository_id_str
spelling 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; charset=utf-82182https://patua.iec.gov.br/bitstreams/31dd8ad4-37b8-4788-b582-26b685ad2bee/download11832eea31b16df8613079d742d61793MD52iec/42002022-10-21 00:46:26.33oai:patua.iec.gov.br:iec/4200https://patua.iec.gov.brRepositório InstitucionalPUBhttps://patua.iec.gov.br/oai/requestclariceneta@iec.gov.br || Biblioteca@iec.gov.bropendoar:2022-10-21T00:46:26Repositório Digital do Instituto Evandro Chagas (Patuá) - Instituto Evandro Chagas (IEC)falsePGI+TGljZW7Dp2EgZGUgRGlzdHJpYnVpw6fDo28gTsOjbyBFeGNsdXNpdmE8L2I+DQoNClRvZG8gZGVwb3NpdGFudGUgZGUgbWF0ZXJpYWwgbm8gUGF0dcOhIGRldmUgY29uY2VkZXIgYW8gSW5zdGl0dXRvIEV2YW5kcm8gQ2hhZ2FzIHVtYSBMaWNlbsOnYSBkZSBEaXN0cmlidWnDp8OjbyBOw6NvIEV4Y2x1c2l2YSBwYXJhIHRvcm5hciBlIG1hbnRlciBhY2Vzc8OtdmVpcyBvcyBzZXVzIGRvY3VtZW50b3MgZW0gZm9ybWF0byBkaWdpdGFsLiANCg0KQ29tIGEgY29uY2Vzc8OjbyBkZXNzYSBsaWNlbsOnYSBuw6NvIGV4Y2x1c2l2YSwgbyBkZXBvc2l0YW50ZSBjb250aW51YSBhIHJldGVyIHRvZG9zIG9zIGRpcmVpdG9zIGRlIGF1dG9yLg0KDQpBbyBhc3NpbmFyIGUgZW50cmVnYXIgZXN0YSBsaWNlbsOnYSB2b2PDqiAoYXV0b3Igb3UgZGV0ZW50b3IgZG9zIGRpcmVpdG9zIGF1dG9yYWlzKQ0KDQphKSBEZWNsYXJhIHF1ZSBjb25oZWNlIGEgcG9sw610aWNhIGRlIGNvcHlyaWdodCBkYSBlZGl0b3JhIGRlIHNldSBkb2N1bWVudG8uDQoNCmIpIENvbmNlZGUgYW8gSW5zdGl0dXRvIEV2YW5kcm8gQ2hhZ2FzIG8gZGlyZWl0byBuw6NvIGV4Y2x1c2l2byBkZSBhcnF1aXZhciwgcmVwcm9kdXppciwgY29udmVydGVyIChjb21vIGRlZmluaWRvIGEgc2VndWlyKSwgY29tdW5pY2FyIGUvb3UgZGlzdHJpYnVpciBubyA8Yj5QYXR1w6E8L2I+LCBvIGRvY3VtZW50byBlbnRyZWd1ZSAoaW5jbHVpbmRvIG8gcmVzdW1vL2Fic3RyYWN0KSBlbSBmb3JtYXRvIGRpZ2l0YWwgb3UgcG9yIHF1YWxxdWVyIG91dHJvIG1laW8uDQoNCmMpIERlY2xhcmEgcXVlIGF1dG9yaXphIG8gSW5zdGl0dXRvIEV2YW5kcm8gQ2hhZ2FzIGEgYXJxdWl2YXIgbWFpcyBkZSB1bWEgY8OzcGlhIGRlc3NlIGRvY3VtZW50byBlIGNvbnZlcnTDqi1sbywgc2VtIGFsdGVyYXIgbyBzZXUgY29udGXDumRvLCBwYXJhIHF1YWxxdWVyIGZvcm1hdG8gZGUgZmljaGVpcm8sIG1laW8gb3Ugc3Vwb3J0ZSwgcGFyYSBlZmVpdG9zIGRlIHNlZ3VyYW7Dp2EsIHByZXNlcnZhw6fDo28gKGJhY2t1cCkgZSBhY2Vzc28uDQoNCmQpIERlY2xhcmEgcXVlIG8gZG9jdW1lbnRvIHN1Ym1ldGlkbyDDqSBvIHNldSB0cmFiYWxobyBvcmlnaW5hbCBlIHF1ZSBkZXTDqW0gbyBkaXJlaXRvIGRlIGNvbmNlZGVyIGEgdGVyY2Vpcm9zIG9zIGRpcmVpdG9zIGNvbnRpZG9zIG5lc3RhIGxpY2Vuw6dhLiBEZWNsYXJhIHRhbWLDqW0gcXVlIGEgZW50cmVnYSBkbyBkb2N1bWVudG8gbsOjbyBpbmZyaW5nZSBvcyBkaXJlaXRvcyBkZSBxdWFscXVlciBvdXRyYSBwZXNzb2Egb3UgZW50aWRhZGUuDQoNCmUpIERlY2xhcmEgcXVlLCBubyBjYXNvIGRvIGRvY3VtZW50byBzdWJtZXRpZG8gY29udGVyIG1hdGVyaWFsIGRvIHF1YWwgbsOjbyBkZXTDqW0gb3MgZGlyZWl0b3MgZGUgYXV0b3IsIG9idGV2ZSBhIGF1dG9yaXphw6fDo28gaXJyZXN0cml0YSBkbyByZXNwZWN0aXZvIGRldGVudG9yIGRlc3NlcyBkaXJlaXRvcywgcGFyYSBjZWRlciBhbyBJbnN0aXR1dG8gRXZhbmRybyBDaGFnYXMgb3MgZGlyZWl0b3MgcmVxdWVyaWRvcyBwb3IgZXN0YSBMaWNlbsOnYSBlIGF1dG9yaXphciBhIHV0aWxpesOhLWxvcyBsZWdhbG1lbnRlLiBEZWNsYXJhIHRhbWLDqW0gcXVlIGVzc2UgbWF0ZXJpYWwgY3Vqb3MgZGlyZWl0b3Mgc8OjbyBkZSB0ZXJjZWlyb3MgZXN0w6EgY2xhcmFtZW50ZSBpZGVudGlmaWNhZG8gZSByZWNvbmhlY2lkbyBubyB0ZXh0byBvdSBjb250ZcO6ZG8gZG8gZG9jdW1lbnRvIGVudHJlZ3VlLg0KDQpmKSBTRSBPIERPQ1VNRU5UTyBFTlRSRUdVRSBGT1IgQkFTRUFETyBFTSBUUkFCQUxITyBGSU5BTkNJQURPIE9VIEFQT0lBRE8gUE9SIE9VVFJBIElOU1RJVFVJw4fDg08gUVVFIE7Dg08gTyBJTlNUSVRVVE8gRVZBTkRSTyBDSEFHQVMsIERFQ0xBUkEgUVVFIENVTVBSSVUgUVVBSVNRVUVSIE9CUklHQcOHw5VFUyBFWElHSURBUyBQRUxPIFJFU1BFQ1RJVk8gQ09OVFJBVE8gT1UgQUNPUkRPLg0KDQpPIEluc3RpdHV0byBFdmFuZHJvIENoYWdhcyBpZGVudGlmaWNhcsOhIGNsYXJhbWVudGUgbyhzKSBub21lKHMpIGRvKHMpIGF1dG9yKGVzKSBkb3MgZGlyZWl0b3MgZG8gZG9jdW1lbnRvIGVudHJlZ3VlIGUgbsOjbyBmYXLDoSBxdWFscXVlciBhbHRlcmHDp8OjbyBhbMOpbSBkbyBwcmV2aXN0byBuYSBhbMOtbmVhIGIpLg==
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
url https://patua.iec.gov.br/handle/iec/4200
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/embargoedAccess
eu_rights_str_mv embargoedAccess
dc.publisher.none.fl_str_mv Taylor & Francis
publisher.none.fl_str_mv Taylor & Francis
dc.source.none.fl_str_mv reponame:Repositório Digital do Instituto Evandro Chagas (Patuá)
instname:Instituto Evandro Chagas (IEC)
instacron:IEC
instname_str Instituto Evandro Chagas (IEC)
instacron_str IEC
institution IEC
reponame_str Repositório Digital do Instituto Evandro Chagas (Patuá)
collection Repositório Digital do Instituto Evandro Chagas (Patuá)
bitstream.url.fl_str_mv https://patua.iec.gov.br/bitstreams/dd8e30fa-2f2f-4f36-9472-7c183d74ed27/download
https://patua.iec.gov.br/bitstreams/1f24c195-a125-46a8-bf66-b00e47162752/download
https://patua.iec.gov.br/bitstreams/ea745466-80bc-4ff2-8c19-c7ba9ba2e361/download
https://patua.iec.gov.br/bitstreams/31dd8ad4-37b8-4788-b582-26b685ad2bee/download
bitstream.checksum.fl_str_mv c9a9c128e29cac82a5d7fdf3f4e6da73
e1c06d85ae7b8b032bef47e42e4c08f9
71859d578212107f7f8c49a4ce09d9ee
11832eea31b16df8613079d742d61793
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
MD5
repository.name.fl_str_mv Repositório Digital do Instituto Evandro Chagas (Patuá) - Instituto Evandro Chagas (IEC)
repository.mail.fl_str_mv clariceneta@iec.gov.br || Biblioteca@iec.gov.br
_version_ 1809190059471011840