Scientific Reports (Dec 2021)

A selective CuII complex with 4-fluorophenoxyacetic acid hydrazide and phenanthroline displays DNA-cleaving and pro-apoptotic properties in cancer cells

  • Pedro Henrique Alves Machado,
  • Drielly Aparecida Paixão,
  • Ricardo Campos Lino,
  • Tiago Rodrigues de Souza,
  • Nayara Júnia de Souza Bontempo,
  • Luana Munique Sousa,
  • Fernanda Van Petten de Vasconcelos Azevedo,
  • Priscila Capelari Orsolin,
  • Paula Marynella Alves Pereira Lima,
  • Isabella Castro Martins,
  • Joyce Ferreira da Costa Guerra,
  • Samuel Cota Teixeira,
  • Thaise Gonçalves Araújo,
  • Luiz Ricardo Goulart,
  • Sandra Morelli,
  • Wendell Guerra,
  • Robson José de Oliveira Júnior

DOI
https://doi.org/10.1038/s41598-021-03909-1
Journal volume & issue
Vol. 11, no. 1
pp. 1 – 15

Abstract

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Abstract The thin line between efficacy and toxicity has challenged cancer therapy. As copper is an essential micronutrient and is important to tumor biology, CuII complexes emerged as an alternative to chemotherapy; however, its biological properties need to be better understood. Thus, we report in vitro the antitumor effects of two CuII complexes named [Cu(4-fh)(phen)(ClO4)2] (complex 1) and [Cu(4-nh)(phen)(ClO4)2]·H2O (complex 2), in which 4-fh = 4-fluorophenoxyacetic acid hydrazide; 4-nh = 4-nitrobenzoic hydrazide and phen = 1,10-phenanthroline. Both complexes presented cytotoxic activity against tumor cells, but only complex 1 showed significant selectivity. Complex 1 also induced DNA-damage, led to G0/G1 arrest and triggered apoptosis, which was initiated by an autophagy dysfunction. The significant in vitro selectivity and the action mechanism of complex 1 are noteworthy and reveal this prodrug as promising for anticancer therapy.