Assessment of the toxicogenic effects and cell death potential of the ester (Z)-methyl 4-((1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)amino)-4-oxobut-2-anoate in combination with cisplatin, cyclophosphamide and doxorubicin

• Autor(a) principal: Juliano Oliveira,Rodrigo
• Data de Publicação: 2019
• Outros Autores: Pereira,Fabrícia Paniago Ajala Nery, Silveira,Ingridhy Ostaciana Maia Freitas da, Lima,Ricardo Vieira de, Berno,Claudia Rodrigues, Pesarini,João Renato, Antoniolli-Silva,Andréia Conceição Milan Brochado, Monreal,Antônio Carlos Duenhas, Adilson,Beatriz, Lima,Dênis Pires de, Gomes,Roberto da Silva
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Genetics and Molecular Biology
• Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572019000300399
• topic: Cancer; 4-aminoantipyrine; 1,4-dioxo-butenyl; chemoprevention; chemotherapy

Abstract Despite rapid advances in both the early detection and treatment of cancer, the mortality from this disease remains high, which justifies the development of new products that are more selective and effective and have fewer side effects. Accordingly, a novel ester was synthesized that contains two pharmacophores with important biological activities: (I) 4-aminoantipyrine, which has anti-inflammatory and antioxidant effects, and (II) the pharmacophore 1,4-dioxo-butenyl, which has cytotoxic activity. When administered alone, this compound is non-genotoxic, and it does not cause an increasing in splenic phagocytosis. Nevertheless, it can induce cell death. When administered in combination with commercial chemotherapeutic agents, such as doxorubicin, cisplatin, and cyclophosphamide, the ester shows antigenotoxic activity and decreases phagocytosis and reduces the potential to cause cell death. These results indicate that the compound should not be used in combination with chemotherapeutic agents that exert their effect through DNA damage, an important feature of antitumor drugs.