1. Distinct effects of novel naphtoquinone-based triazoles in human leukaemic cell lines.
- Author
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Coulidiati TH, Dantas BB, Faheina-Martins GV, Gonçalves JC, do Nascimento WS, de Oliveira RN, Camara CA, Oliveira EJ, Lara A, Gomes ER, and Araújo DA
- Subjects
- Antineoplastic Agents chemistry, Apoptosis drug effects, Apoptosis Regulatory Proteins metabolism, Cell Cycle Proteins metabolism, Cell Proliferation drug effects, Cell Survival drug effects, DNA Fragmentation, Dose-Response Relationship, Drug, HL-60 Cells, Humans, Inhibitory Concentration 50, K562 Cells, Leukemia metabolism, Leukemia pathology, Membrane Potential, Mitochondrial drug effects, Molecular Structure, Naphthoquinones chemistry, Oxidative Stress drug effects, Reactive Oxygen Species metabolism, S Phase Cell Cycle Checkpoints drug effects, Structure-Activity Relationship, Triazoles chemistry, Antineoplastic Agents pharmacology, Leukemia drug therapy, Naphthoquinones pharmacology, Triazoles pharmacology
- Abstract
Objectives: 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., Key Findings: 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., Conclusion: Taken together our results showed that C2 and C3 triazole derivatives presented the best potential for drug design., (© 2015 Royal Pharmaceutical Society.)
- Published
- 2015
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