New Bis copper complex ((Z) -4 - ((4-chlorophenyl) amino) -4-oxobut-2-enoyl) oxy): Cytotoxicity in 4T1 cells and their toxicogenic potential in Swiss mice.

Toxicol Appl Pharmacol

Centro de Estudos em Células Tronco, Terapia Celular e Genética Toxicológica - CeTroGen, Hospital Universitário Maria Aparecida Pedrossian, Empresa Brasileira de Serviços Hospitalares - EBSERH, Campo Grande, Mato Grosso do Sul, Brazil; Programa de Pós-graduação em Genética e Biologia Molecular, Centro de Ciências Biológicas - CCB, Departamento de Biologia Geral, Universidade Estadual de Londrina - UEL, Londrina, Brazil.; Programa de Mestrado em Farmácia, Faculdade de Ciências Farmacêuticas, Alimentos e Nutrição - FACFAN, Universidade Federal de Mato Grosso do Sul - UFMS, Campo Grande, Mato Grosso do Sul, Brazil; Faculdade de Medicina Dr. Hélio Mandetta, Programa de Pós-graduação em Saúde e Desenvolvimento na Região Centro-Oeste, Campo Grande, Mato Grosso do Sul, Brazil. Electronic address:

Published: October 2018

Copper (II) complexes are promising in the development of new synthetic models for cancer treatment. In this context, we synthesized a new copper complex containing the pharmacophore group 1,4-dioxo-2-butenyl, the Bis(((Z)-4-((4-chlorophenyl) amino)-4-oxobut-2-enoyl)oxy) copper compound and we evaluated its antitumor activity in 4 T1 murine mammary adenocarcinoma cells and their toxicogenic effect in Swiss mice. The compound demonstrated cytotoxicity and genotoxicity to 4 T1 cells, and after cell cycle arrest in G1, which occurred by the increase in ATM and p21 expression, it induced the cells to apoptosis by increasing BAX and caspase-7. In vivo the compound was genotoxic in mice but did not show permanent damage, observed by the absence of increased micronucleus frequency, and did not induce changes in the biometric parameters of the animals. These results indicate that the new copper complex, described firstly in this work, presents therapeutic potential for breast cancer.

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http://dx.doi.org/10.1016/j.taap.2018.08.004DOI Listing

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