Rubrolide analogues and their derived lactams as potential anticancer agents

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dc.creatorUlisses Alves Pereira
dc.creatorThaís Altoé Moreira
dc.creatorLuiz Cláudio de Almeida Barbosa
dc.creatorCélia Regina Álvares Maltha
dc.creatorIgor da Silva Bomfim
dc.creatorSarah Sant' Anna Maranhão
dc.creatorManoel Odorico de Moraes Filho
dc.creatorClaudia do Ó Pessoa
dc.creatorFrancisco Washington Araújo Barros Nepomuceno
dc.date.accessioned2022-09-22T18:41:24Z
dc.date.accessioned2025-09-09T00:52:58Z
dc.date.available2022-09-22T18:41:24Z
dc.date.issued2016
dc.description.sponsorshipCNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico
dc.description.sponsorshipFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais
dc.description.sponsorshipCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
dc.description.sponsorshipFINEP - Financiadora de Estudos e Projetos, Financiadora de Estudos e Projetos
dc.description.sponsorshipOutra Agência
dc.identifier.doihttps://doi.org/10.1039/C5MD00459D
dc.identifier.issn2040-2511
dc.identifier.urihttps://hdl.handle.net/1843/45390
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofMedChemComm
dc.rightsAcesso Restrito
dc.subjectSíntese orgânica
dc.subjectQuímica orgânica
dc.subjectLactonas
dc.subjectCâncer
dc.subjectMorte celular
dc.subjectApoptose
dc.titleRubrolide analogues and their derived lactams as potential anticancer agents
dc.typeArtigo de periódico
local.citation.epage352
local.citation.spage345
local.citation.volume7
local.description.resumoSeven β-aryl-substituted γ-alkylidene-γ-lactone analogues of rubrolides were synthesized from mucochloric acid and converted into their corresponding γ-hydroxy-γ-lactams (76–85%) by a reaction with isobutylamine and propylamine. Further dehydration of the γ-hydroxy-γ-lactams led to the corresponding (Z)- and (E)-γ-alkylidene-γ-lactams (23–45%). All compounds were fully characterized by spectroscopic methods. These 14 compounds, together with 32 other rubrolide analogues, were assayed against four human tumor cell lines (HL-60, leukaemia; HCT-116, colon; SF-295, central nervous system; and OVCAR-8, ovarian). Of the 46 compounds assayed, 7 caused a large reduction in cell viability (% RCV > 80%) in the tested cell lines and the most active compounds had halogen substituents on the aromatic ring. Compounds 10a and 14i were the most active (RC50 = 3.00 and 3.58 μM, respectively) against HL-60 and were not cytotoxic to L929 normal cells at the concentrations tested (RC50 > 50 μM). To further understand the mechanism underlying the cytotoxicity of 10a and 14i, studies involving DNA fragmentation, cell cycle analysis, phosphatidyl serine externalization and mitochondrial depolarization were performed in the HL-60 cells, using doxorubicin as a positive control. The results indicated that the cytotoxicity of 10a and 14i involved the induction of cell death by apoptosis. The cell cycle analysis showed that 14i caused the accumulation of cells in the G0/G1 phase at 2.5 and 5 μM.
local.publisher.countryBrasil
local.publisher.departmentICA - INSTITUTO DE CIÊNCIAS AGRÁRIAS
local.publisher.initialsUFMG
local.url.externahttps://pubs.rsc.org/en/content/articlelanding/2016/md/c5md00459d

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