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

dc.creatorSantos, Daiane Fernanda dos
dc.creatorPilger, Denise Regina Bairros de
dc.creatorVandermeulen, Charlotte
dc.creatorCunha, Antonio Ricardo Khouri
dc.creatorMantoani, Susimaire Pedersoli
dc.creatorNunes, Paulo Sérgio Gonçalves
dc.creatorAndrade, Peterson de
dc.creatorCarvalho, Ivone
dc.creatorCasseb, Jorge
dc.creatorTwizere, Jean-Claude
dc.creatorWillems, Luc
dc.creatorFreitas Junior, Lucio
dc.creatorKashima, Simone
dc.date2020-10-26T17:09:23Z
dc.date2020-10-26T17:09:23Z
dc.date2020
dc.date.accessioned2023-09-26T23:24:03Z
dc.date.available2023-09-26T23:24:03Z
dc.identifierSANTOS, 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.identifier0968-0896
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/44203
dc.identifier10.1016/j.bmc.2020.115746
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8890169
dc.descriptionFundação 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).
dc.descriptionHuman 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherElsevier
dc.rightsopen access
dc.subjectHTLV-1
dc.subjectATL
dc.subjectTriagem
dc.subjectProliferação celular
dc.subjectApoptose
dc.subjectProteína
dc.subjectHTLV-1
dc.subjectATL
dc.subjectCompound screening
dc.subjectCell proliferation
dc.subjectApoptosis
dc.subjectTax protein
dc.titleNon-cytotoxic 1,2,3-triazole tethered fused heterocyclic ring derivatives display Tax protein inhibition and impair HTLV-1 infected cells
dc.typeArticle


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