Non-cytotoxic 1,2,3-triazole tethered fused heterocyclic ring derivatives display Tax protein inhibition and impair HTLV-1 infected cells
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
Texto Completo: | https://www.arca.fiocruz.br/handle/icict/44203 |
Resumo: | Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, n. 2015/11566-0 and n. 2016/17301-1) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, n. 462290/2014-0). |
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Santos, Daiane Fernanda dosPilger, Denise Regina Bairros deVandermeulen, CharlotteCunha, Antonio Ricardo KhouriMantoani, Susimaire PedersoliNunes, Paulo Sérgio GonçalvesAndrade, Peterson deCarvalho, IvoneCasseb, JorgeTwizere, Jean-ClaudeWillems, LucFreitas Junior, LucioKashima, Simone2020-10-26T17:09:23Z2020-10-26T17:09:23Z2020SANTOS, Daiane Fernanda dos et al. Non-cytotoxic 1,2,3-triazole tethered fused heterocyclic ring derivatives display Tax protein inhibition and impair HTLV-1 infected cells. Bioorganic and Medicinal Chemistry, 2020.0968-0896https://www.arca.fiocruz.br/handle/icict/4420310.1016/j.bmc.2020.115746Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, n. 2015/11566-0 and n. 2016/17301-1) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, n. 462290/2014-0).University of São Paulo. Ribeirão Preto Medical School. Ribeirão Preto, SP, Brazil / Regional Blood Center of Ribeirão Preto. Ribeirão Preto, SP, Brazil.Federal University of São Paulo. São Paulo, SP, Brazil / University of São Paulo. Biomedical Sciences Institute. Department of Microbiology. São Paulo, SP, Brazil.University of Liège. Protein Signaling and Interactions. Liège, Belgium.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.University of São Paulo. School of Pharmaceutical Sciences of Ribeirão Preto. Ribeirão Preto, SP, Brazil.University of São Paulo. School of Pharmaceutical Sciences of Ribeirão Preto. Ribeirão Preto, SP, Brazil.University of São Paulo. School of Pharmaceutical Sciences of Ribeirão Preto. Ribeirão Preto, SP, Brazil.University of São Paulo. School of Pharmaceutical Sciences of Ribeirão Preto. Ribeirão Preto, SP, Brazil.University of São Paulo.In stitute of Tropical Medicine of São Paulo. São Paulo, SP, Brazil.University of Liège. Protein Signaling and Interactions. Liège, Belgium.University of Liège, Molecular and Cellular Epigenetics. Liège, Belgium.University of São Paulo. Biomedical Sciences Institute. Department of Microbiology. São Paulo, SP, Brazil.University of São Paulo. Ribeirão Preto Medical School. Ribeirão Preto, SP, Brazil / Regional Blood Center of Ribeirão Preto. Ribeirão Preto, SP, Brazil.Human T cell lymphotropic virus type 1 (HTLV-1) is a human retrovirus that infects approximately 10–20 million people worldwide and causes an aggressive neoplasia (adult T-cell leukemia/lymphoma - ATL). Therapeutic approaches for the treatment of ATL have variable effectiveness and poor prognosis, thus requiring strategies to identify novel compounds with activity on infected cells. In this sense, we initially screened a small series of 25 1,2,3-triazole derivatives to discover cell proliferation inhibitors and apoptosis inducers in HTLV-1- infected T-cell line (MT-2) for further assessment of their effect on viral tax activity through inducible-tax reporter cell line (Jurkat LTR-GFP). Eight promising compounds (02, 05, 06, 13, 15, 21, 22 and 25) with activity ≥70% were initially selected, based on a suitable cell-based assay using resazurin reduction method, and evaluated towards cell cycle, apoptosis and Tax/GFP expression analyses through flow cytometry. Compound 02 induced S phase cell cycle arrest and compounds 05, 06, 22 and 25 promoted apoptosis. Remarkably, compounds 22 and 25 also reduced GFP expression in an inducible-tax reporter cell, which suggests an effect on Tax viral protein. More importantly, compounds 02, 22 and 25 were not cytotoxic in human hepatoma cell line (Huh-7). Therefore, the discovery of 3 active and non-cytotoxic compounds against HTLV-1-infected cells can potentially contribute, as an initial promising strategy, to the development process of new drugs against ATL.engElsevierHTLV-1ATLTriagemProliferação celularApoptoseProteínaHTLV-1ATLCompound screeningCell proliferationApoptosisTax proteinNon-cytotoxic 1,2,3-triazole tethered fused heterocyclic ring derivatives display Tax protein inhibition and impair HTLV-1 infected cellsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83097https://www.arca.fiocruz.br/bitstream/icict/44203/1/license.txt36b51ef91c52b5338d9d29ba0cc807bcMD51ORIGINALSantos, Daiane Fernanda. Non-cytotoxic....pdfSantos, Daiane Fernanda. Non-cytotoxic....pdfapplication/pdf3645645https://www.arca.fiocruz.br/bitstream/icict/44203/2/Santos%2c%20Daiane%20Fernanda.%20Non-cytotoxic....pdf1c8b964e3bc9b0caedbf4d3266ed6749MD52TEXTSantos, Daiane Fernanda. Non-cytotoxic....pdf.txtSantos, Daiane Fernanda. Non-cytotoxic....pdf.txtExtracted texttext/plain51291https://www.arca.fiocruz.br/bitstream/icict/44203/3/Santos%2c%20Daiane%20Fernanda.%20Non-cytotoxic....pdf.txted481db25c85a842a11abd85f34c7058MD53icict/442032023-03-15 14:34:16.883oai:www.arca.fiocruz.br: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Repositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-03-15T17:34:16Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
dc.title.pt_BR.fl_str_mv |
Non-cytotoxic 1,2,3-triazole tethered fused heterocyclic ring derivatives display Tax protein inhibition and impair HTLV-1 infected cells |
title |
Non-cytotoxic 1,2,3-triazole tethered fused heterocyclic ring derivatives display Tax protein inhibition and impair HTLV-1 infected cells |
spellingShingle |
Non-cytotoxic 1,2,3-triazole tethered fused heterocyclic ring derivatives display Tax protein inhibition and impair HTLV-1 infected cells Santos, Daiane Fernanda dos HTLV-1 ATL Triagem Proliferação celular Apoptose Proteína HTLV-1 ATL Compound screening Cell proliferation Apoptosis Tax protein |
title_short |
Non-cytotoxic 1,2,3-triazole tethered fused heterocyclic ring derivatives display Tax protein inhibition and impair HTLV-1 infected cells |
title_full |
Non-cytotoxic 1,2,3-triazole tethered fused heterocyclic ring derivatives display Tax protein inhibition and impair HTLV-1 infected cells |
title_fullStr |
Non-cytotoxic 1,2,3-triazole tethered fused heterocyclic ring derivatives display Tax protein inhibition and impair HTLV-1 infected cells |
title_full_unstemmed |
Non-cytotoxic 1,2,3-triazole tethered fused heterocyclic ring derivatives display Tax protein inhibition and impair HTLV-1 infected cells |
title_sort |
Non-cytotoxic 1,2,3-triazole tethered fused heterocyclic ring derivatives display Tax protein inhibition and impair HTLV-1 infected cells |
author |
Santos, Daiane Fernanda dos |
author_facet |
Santos, Daiane Fernanda dos Pilger, Denise Regina Bairros de Vandermeulen, Charlotte Cunha, Antonio Ricardo Khouri Mantoani, Susimaire Pedersoli Nunes, Paulo Sérgio Gonçalves Andrade, Peterson de Carvalho, Ivone Casseb, Jorge Twizere, Jean-Claude Willems, Luc Freitas Junior, Lucio Kashima, Simone |
author_role |
author |
author2 |
Pilger, Denise Regina Bairros de Vandermeulen, Charlotte Cunha, Antonio Ricardo Khouri Mantoani, Susimaire Pedersoli Nunes, Paulo Sérgio Gonçalves Andrade, Peterson de Carvalho, Ivone Casseb, Jorge Twizere, Jean-Claude Willems, Luc Freitas Junior, Lucio Kashima, Simone |
author2_role |
author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Santos, Daiane Fernanda dos Pilger, Denise Regina Bairros de Vandermeulen, Charlotte Cunha, Antonio Ricardo Khouri Mantoani, Susimaire Pedersoli Nunes, Paulo Sérgio Gonçalves Andrade, Peterson de Carvalho, Ivone Casseb, Jorge Twizere, Jean-Claude Willems, Luc Freitas Junior, Lucio Kashima, Simone |
dc.subject.other.pt_BR.fl_str_mv |
HTLV-1 ATL Triagem Proliferação celular Apoptose Proteína |
topic |
HTLV-1 ATL Triagem Proliferação celular Apoptose Proteína HTLV-1 ATL Compound screening Cell proliferation Apoptosis Tax protein |
dc.subject.en.pt_BR.fl_str_mv |
HTLV-1 ATL Compound screening Cell proliferation Apoptosis Tax protein |
description |
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, n. 2015/11566-0 and n. 2016/17301-1) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, n. 462290/2014-0). |
publishDate |
2020 |
dc.date.accessioned.fl_str_mv |
2020-10-26T17:09:23Z |
dc.date.available.fl_str_mv |
2020-10-26T17:09:23Z |
dc.date.issued.fl_str_mv |
2020 |
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 |
SANTOS, Daiane Fernanda dos et al. Non-cytotoxic 1,2,3-triazole tethered fused heterocyclic ring derivatives display Tax protein inhibition and impair HTLV-1 infected cells. Bioorganic and Medicinal Chemistry, 2020. |
dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/44203 |
dc.identifier.issn.pt_BR.fl_str_mv |
0968-0896 |
dc.identifier.doi.none.fl_str_mv |
10.1016/j.bmc.2020.115746 |
identifier_str_mv |
SANTOS, Daiane Fernanda dos et al. Non-cytotoxic 1,2,3-triazole tethered fused heterocyclic ring derivatives display Tax protein inhibition and impair HTLV-1 infected cells. Bioorganic and Medicinal Chemistry, 2020. 0968-0896 10.1016/j.bmc.2020.115746 |
url |
https://www.arca.fiocruz.br/handle/icict/44203 |
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eng |
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eng |
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info:eu-repo/semantics/openAccess |
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openAccess |
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Elsevier |
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Elsevier |
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reponame:Repositório Institucional da FIOCRUZ (ARCA) instname:Fundação Oswaldo Cruz (FIOCRUZ) instacron:FIOCRUZ |
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Repositório Institucional da FIOCRUZ (ARCA) |
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