Non-cytotoxic 1,2,3-triazole tethered fused heterocyclic ring derivatives display Tax protein inhibition and impair HTLV-1 infected cells

Detalhes bibliográficos
Autor(a) principal: Santos, Daiane Fernanda dos
Data de Publicação: 2020
Outros Autores: 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
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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spelling 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. 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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
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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