title: Distinct effects of novel naphtoquinone-based triazoles in human leukaemic cell lines.
abstract: OBJECTIVE
  The aim of this study was to investigate the cytotoxic effect of new 1,4-naphthoquinone- 1,2,3-triazoles, named C2 to C8 triazole derivatives, towards human cancer cell lines.
  
  
  METHODS
  The effect on cell viability was assessed by MTT and propidium iodide assays. The cytotoxic effect of C2 and C3 in K562 and HL-60 cells were analyzed by flow cytometry, DNA fragmentation and reactive oxygen species (ROS) production. Western blot and q-PCR procedures were also performed.
  
  
  RESULTS
  C2 and C3 inhibited both K562 and HL-60 cells growth in a concentration-dependent manner. C2 presented the highest cytotoxic activity with an IC50 of approximately 14 μm and 41 μm for HL-60 and K562 cells, respectively, while being less toxic to normal peripheral blood monocyte cells. Both derivatives induced cellular changes in HL-60 cells, characteristic of apoptosis, such as mitochondrial membrane depolarization, phosphatidylserine externalization, increasing sub-G1 phase, DNA fragmentation, downregulating Bcl-2 protein and upregulating Bax protein. In K562 cells, C2 and C3 induced S-phase arrest of cell cycle, which was associated with upregulation of p21. The effect of these derivatives in HL-60 cells can be related to the ROS intracellular level.
  
  
  CONCLUSIONS
  Taken together our results showed that C2 and C3 triazole derivatives presented the best potential for drug design.
authors.affiliation: Departamento de Biotecnologia, Centro de Biotecnologia, Universidade Federal da Paraíba, João Pessoa, Brazil.
authors.forename: Tangbadioa H
authors.initials: TH
authors.lastname: Coulidiati
authors.affiliation: Departamento de Biotecnologia, Centro de Biotecnologia, Universidade Federal da Paraíba, João Pessoa, Brazil.
authors.forename: Bruna B
authors.initials: BB
authors.lastname: Dantas
authors.affiliation: Departamento de Biotecnologia, Centro de Biotecnologia, Universidade Federal da Paraíba, João Pessoa, Brazil.
authors.forename: Glaucia V
authors.initials: GV
authors.lastname: Faheina-Martins
authors.affiliation: Departamento de Biotecnologia, Centro de Biotecnologia, Universidade Federal da Paraíba, João Pessoa, Brazil.
authors.forename: Juan C R
authors.initials: JC
authors.lastname: Gonçalves
authors.affiliation: Laboratório de Síntese de Compostos Bioativos, Departamento de Ciências Moleculares, Universidade Federal Rural de Pernambuco, Recife, Brazil.
authors.forename: Wilson S
authors.initials: WS
authors.lastname: do Nascimento
authors.affiliation: Laboratório de Síntese de Compostos Bioativos, Departamento de Ciências Moleculares, Universidade Federal Rural de Pernambuco, Recife, Brazil.
authors.forename: Ronaldo N
authors.initials: RN
authors.lastname: de Oliveira
authors.affiliation: Laboratório de Síntese de Compostos Bioativos, Departamento de Ciências Moleculares, Universidade Federal Rural de Pernambuco, Recife, Brazil.
authors.forename: Celso A
authors.initials: CA
authors.lastname: Camara
authors.affiliation: Departamento de Biotecnologia, Centro de Biotecnologia, Universidade Federal da Paraíba, João Pessoa, Brazil.
authors.forename: Eduardo J
authors.initials: EJ
authors.lastname: Oliveira
authors.affiliation: Departamento de Biotecnologia, Centro de Biotecnologia, Universidade Federal da Paraíba, João Pessoa, Brazil.
authors.forename: Aline
authors.initials: A
authors.lastname: Lara
authors.affiliation: Departamento de Biotecnologia, Centro de Biotecnologia, Universidade Federal da Paraíba, João Pessoa, Brazil.
authors.forename: Eneas R
authors.initials: ER
authors.lastname: Gomes
authors.affiliation: Departamento de Biotecnologia, Centro de Biotecnologia, Universidade Federal da Paraíba, João Pessoa, Brazil.
authors.forename: Demetrius A M
authors.initials: DA
authors.lastname: Araújo
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D015394:Molecular Structure; D009285:Naphthoquinones / Q000737:chemistry / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D009285:Naphthoquinones; D017382:Reactive Oxygen Species; D014230:Triazoles; C035342:1,4-naphthoquinone
keywords: 1,4-naphthoquinone-1,2,3-triazoles; apoptosis; cytotoxicity; flow cytometry; leukaemic cells