2. Academic Validation
  3. Novel pyrimidinic selenourea induces DNA damage, cell cycle arrest, and apoptosis in human breast carcinoma

Novel pyrimidinic selenourea induces DNA damage, cell cycle arrest, and apoptosis in human breast carcinoma

  • Eur J Med Chem. 2018 Jul 15:155:503-515. doi: 10.1016/j.ejmech.2018.06.026.
Flavio A R Barbosa 1,  Tâmila Siminski 2,  Rômulo F S Canto 3,  Gabriela M Almeida 2,  Nádia S R S Mota 2,  Fabiana Ourique 2,  Rozangela Curi Pedrosa 4,  Antonio Luiz Braga 5
Affiliations

Affiliations

  • 1 Laboratório de Síntese de Substâncias de Selênio Bioativas (LabSelen), Departamento de Química, Universidade Federal de Santa Catarina (UFSC), Florianópolis, SC, Brazil.
  • 2 Laboratório de Bioquímica Experimental (LABIOEX), Departamento de Bioquímica, Universidade Federal de Santa Catarina (UFSC), Florianópolis, SC, Brazil.
  • 3 Laboratório de Química Medicinal de Compostos de Selênio (QMCSe), Programa de pós-graduação em Ciências da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil.
  • 4 Laboratório de Bioquímica Experimental (LABIOEX), Departamento de Bioquímica, Universidade Federal de Santa Catarina (UFSC), Florianópolis, SC, Brazil. Electronic address: rozangela.pedrosa@ufsc.br.
  • 5 Laboratório de Síntese de Substâncias de Selênio Bioativas (LabSelen), Departamento de Química, Universidade Federal de Santa Catarina (UFSC), Florianópolis, SC, Brazil. Electronic address: braga.antonio@ufsc.br.
PMID: 29908443 DOI: 10.1016/j.ejmech.2018.06.026
Abstract

Novel pyrimidinic selenoureas were synthesized and evaluated against tumour and normal cell lines. Among these, the compound named 3j initially showed relevant cytotoxicity and selectivity for tumour cells. Three analogues of 3j were designed and synthesized keeping in view the structural requirements of this compound. Almost all the tested compounds displayed considerable cytotoxicity. However, 8a, one of the 3j analogues, was shown to be highly selective and cytotoxic, especially for breast carcinoma cells (MCF-7) (IC50 = 3.9 μM). Furthermore, 8a caused DNA damage, inhibited cell proliferation, was able to arrest cell cycle in S phase, and induced cell death by Apoptosis in human breast carcinoma cells. Moreover, predictions of pharmacokinetic properties showed that 8a may present good absorption and permeation characteristics for oral administration. Overall, the current study established 8a as a potential drug prototype to be employed as a DNA interactive cytotoxic agent for the treatment of breast Cancer.

Keywords

Apoptosis; Cell cycle arrest; Cytotoxicity; DNA damage; Dihydropyrimidinones; Organoselenium; Selenoureas.

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