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Cytotoxicity, genotoxicity and mutagenicity of mixed ternary mononuclear Mg complex based on valproic acid with 1,10-phenanthroline in Saccharomyces cerevisiae and V79 cells.
Vanini, Julia; Rodrigues, Gabriel Berbigier; Juchem, André Luiz Mendes; Guecheva, Temenouga Nikolova; Moura, Sidnei; Dumas, Françoise; Henriques, João Antonio Pêgas; de Oliveira, Iuri Marques.
Afiliação
  • Vanini J; Department of Biophysics, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
  • Rodrigues GB; Department of Biophysics, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
  • Juchem ALM; Department of Biophysics, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
  • Guecheva TN; Department of Biophysics, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
  • Moura S; Institute of Molecular Biology "Rumen Tsanev", Bulgarian Academy of Sciences, Sofia, Bulgaria.
  • Dumas F; Laboratory of Natural and Synthetics Products, University of Caxias do Sul, Caxias do Sul, RS, Brazil.
  • Henriques JAP; Laboratoire BioCIS, CNRS UMR 8076, Université Paris Saclay, France.
  • de Oliveira IM; Department of Biophysics, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
Article em En | MEDLINE | ID: mdl-39364577
ABSTRACT
Valproic acid (VA) is a widely used drug for the treatment of diseases affecting the central nervous system. Due to its epigenetic modulatory potential, it has been studied for possible therapeutic application in anticancer therapies. However, the VA exhibits different side effects in its application. Thus, synthetic coordination complexes with valproate can generate promising candidates for new active drugs with reduced toxicity. In this sense, we investigated the genotoxic and mutagenic potential of the sodium valproate and of the mixed ternary mononuclear Mg complex based on VA with 1,10-phenanthroline (Phen) ligand - [Mg (Valp)2Phen], in Saccharomyces cerevisiae and V79 cells. The MTT and clonal survival assays in V79 cells indicated that the Mg complex has higher cytotoxicity than sodium valproate. A similar cytotoxicity profile is observed in yeast. This fact is possibly due to the intercalation capacity of [Mg(Valp)2Phen], inducing DNA strand breaks, as observed in the comet assay and micronucleus test. In this sense, members of the NER, HR, NHEJ and TLS repair pathways are required for the repair of DNA lesions induced by [Mg(Valp)2Phen]. Interestingly, BER proteins apparently increase the cytotoxic potential of the drug. Furthermore, the [Mg(Valp)2Phen] showed higher cytotoxicity in V79 cells and yeast when compared to sodium valproate indicating applicability as a cytotoxic agent.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Basic Clin Pharmacol Toxicol Assunto da revista: FARMACOLOGIA / TOXICOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Basic Clin Pharmacol Toxicol Assunto da revista: FARMACOLOGIA / TOXICOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido