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Please use this identifier to cite or link to this item: http://hdl.handle.net/1843/72626
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dc.creatorLarissa de Oliveira Passos Jesuspt_BR
dc.creatorAline Aparecida de Souzapt_BR
dc.creatorHeron Fernandes Vieira Torquatopt_BR
dc.creatorVanessa Silva Gontijopt_BR
dc.creatorRossimiriam Pereira de Freitaspt_BR
dc.creatorTarsis Ferreira Gesteirapt_BR
dc.creatorVivien Jane Coulson-Thomaspt_BR
dc.creatorRicardo José Soares Torquatopt_BR
dc.creatorAparecida Sadae Tanakapt_BR
dc.creatorEdgar Julian Paredes-Gameropt_BR
dc.creatorWagner Alves de Souza Judicept_BR
dc.date.accessioned2024-08-05T17:44:46Z-
dc.date.available2024-08-05T17:44:46Z-
dc.date.issued2022-
dc.citation.volume27pt_BR
dc.citation.issue23pt_BR
dc.identifier.doihttps://doi.org/10.3390/molecules27238633pt_BR
dc.identifier.issn1420-3049pt_BR
dc.identifier.urihttp://hdl.handle.net/1843/72626-
dc.description.resumoThis study investigates the efficacy of miltefosine, alkylphospholipid, and alkyltriazolederivative compounds against leukemia lineages. The cytotoxic effects and cellular and molecular mechanisms of the compounds were investigated. The inhibitory potential and mechanism of inhibition of cathepsins B and L, molecular docking simulation, molecular dynamics and binding free energy evaluation were performed to determine the interaction of cathepsins and compounds. Among the 21 compounds tested, C9 and C21 mainly showed cytotoxic effects in Jurkat and CCRF-CEM cells, two human acute lymphoblastic leukemia (ALL) lineages. Activation of induced cell death by C9 and C21 with apoptotic and necrosis-like characteristics was observed, including an increase in annexin-V+propidium iodide−, annexin-V+propidium iodide+, cleaved caspase 3 and PARP, cytochrome c release, and nuclear alterations. Bax inhibitor, Z-VAD-FMK, pepstatin, and necrostatin partially reduced cell death, suggesting that involvement of the caspase-dependent and -independent mechanisms is related to cell type. Compounds C9 and C21 inhibited cathepsin L by a noncompetitive mechanism, and cathepsin B by a competitive and noncompetitive mechanism, respectively. Complexes cathepsin-C9 and cathepsin-C21 exhibited significant hydrophobic interactions, water bridges, and hydrogen bonds. In conclusion, alkyltriazoles present cytotoxic activity against acute lymphoblastic lineages and represent a promising scaffold for the development of molecules for this application.pt_BR
dc.description.sponsorshipCNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológicopt_BR
dc.description.sponsorshipCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorpt_BR
dc.description.sponsorshipOutra Agênciapt_BR
dc.format.mimetypepdfpt_BR
dc.languageengpt_BR
dc.publisherUniversidade Federal de Minas Geraispt_BR
dc.publisher.countryBrasilpt_BR
dc.publisher.departmentICX - DEPARTAMENTO DE QUÍMICApt_BR
dc.publisher.initialsUFMGpt_BR
dc.relation.ispartofMoleculespt_BR
dc.rightsAcesso Abertopt_BR
dc.subjectAlkylphospholipidspt_BR
dc.subjectAlkyltriazolespt_BR
dc.subjectCell deathpt_BR
dc.subjectAcute lymphoblastic leukemiapt_BR
dc.subjectCathepsin inhibitionpt_BR
dc.subject.otherAgentes antineoplásicospt_BR
dc.subject.otherLeucemia linfoblásticapt_BR
dc.subject.otherCélulas mortaspt_BR
dc.subject.otherDinâmica molecularpt_BR
dc.titleIn vitro study of cytotoxic mechanisms of alkylphospholipids and alkyltriazoles in acute lymphoblastic leukemia modelspt_BR
dc.typeArtigo de Periódicopt_BR
dc.url.externahttps://www.mdpi.com/1420-3049/27/23/8633pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0001-9004-4872pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0002-9480-9657pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0003-1674-818Xpt_BR
dc.identifier.orcidhttps://orcid.org/0000-0001-6974-3724pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0002-0136-0986pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0002-5848-0225pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0001-9407-805Xpt_BR
dc.identifier.orcidhttps://orcid.org/0000-0003-3686-8402pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0002-1608-9105pt_BR
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