Hydrazones as novel epigenetic modulators: Correlation between TET 1 protein inhibition activity and their iron(II) binding ability |
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| Institution: | 1. Núcleo de Estudo e Pesquisa em Histopatologia, Departamento de Ciências da Vida, Universidade Estadual da Bahia, CEP 41150-000 Salvador, BA, Brazil;2. Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), CEP 40296-710 Salvador, BA, Brazil;3. Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBio®), Universidade Federal do Rio de Janeiro, CEP 21941-971 Rio de Janeiro, RJ, Brazil;4. Instituto de Bioquímica Médica Leopoldo de Meis, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, CEP 21941-590 Rio de Janeiro, RJ, Brazil;5. Centro de Biotecnologia e Terapia Celular, Hospital São Rafael, CEP 41253-190 Salvador, BA, Brazil |
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| Abstract: | Ten-eleven translocation protein (TET) 1 plays a key role in control of DNA demethylation and thereby of gene expression. Dysregulation of these processes leads to serious pathological states such as oncological and neurodegenerative ones and thus TET 1 targeting is highly requested. Therefore, in this work, we examined the ability of hydrazones (acyl-, aroyl- and heterocyclic hydrazones) to inhibit the TET 1 protein and its mechanism of action. Inhibitory activity of hydrazones 1–7 towards TET 1 was measured. The results showed a high affinity of the tested chelators for iron(II). The study clearly showed a significant correlation between the chelator’s affinity for iron(II) ions (represented by the binding constant) and TET 1 protein inhibitory activity (represented by IC50 values). |
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| Keywords: | Epigenetic Hydrazone Inhibitor Iron(II) affinity TET 1 protein |
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