Revista: | Genetics and molecular biology |
Base de datos: | PERIÓDICA |
Número de sistema: | 000417979 |
ISSN: | 1415-4757 |
Autores: | Oliveira, Rodrigo Juliano1 Santos, Naiara da Cruz Leite2 Pesarini, Joao Renato3 Oliveira, Beatriz Carneiro de1 Berno, Claudia Rodrigues1 Araujo, Flavio Henrique Souza de2 Silveira, Ingridhy Ostaciana Maia Freitas da4 Nascimento, Raquel Oliveira5 Antoniolli-Silva, Andreia Conceicao Milan Brochado3 Monreal, Antonio Carlos Duenhas2 Beatriz, Adilson4 Lima, Denis Pires de2 Gomes, Roberto da Silva5 |
Instituciones: | 1Universidade Federal de Mato Grosso do Sul, Centro de Estudos em Celulas Tronco, Terapia Celular, e Genetica Toxicologica, Campo Grande, Mato Grosso do Sul. Brasil 2Universidade Federal de Mato Grosso do Sul, Centro de Ciencias Biologicas e da Saude, Campo Grande, Mato Grosso do Sul. Brasil 3Universidade Federal de Mato Grosso do Sul, Programa de Pos-Graduacao em Saude e Desenvolvimento na Regiao Centro-Oeste, Campo Grande, Mato Grosso do Sul. Brasil 4Universidade Federal de Mato Grosso do Sul, Programa de Pos-Graduacao em Quimica, Campo Grande, Mato Grosso do Sul. Brasil 5Universidade Federal da Grande Dourados, Faculdade de Ciencias Exatas e Tecnologia, Dourados, Mato Grosso do Sul. Brasil |
Año: | 2018 |
Periodo: | Mar |
Volumen: | 41 |
Número: | 1 |
Paginación: | 154-166 |
País: | Brasil |
Idioma: | Inglés |
Tipo de documento: | Artículo |
Enfoque: | Experimental |
Resumen en inglés | The increased incidence of cancer and its high treatment costs have encouraged the search for new compounds to be used in adjuvant therapies for this disease. This study discloses the synthesis of (Z)-4-((1,5-dimethyl-3-oxo2-phenyl-2,3dihydro-1H-pyrazol-4-yl) amino)-4-oxobut-2-enoic acid (IR-01) and evaluates not only the action of this compound on genetic integrity, increase in splenic phagocytosis and induction of cell death but also its effects in combination with the commercial chemotherapeutic agents doxorubicin, cisplatin and cyclophosphamide. IR-01 was designed and synthesized based on two multifunctionalyzed structural fragments: 4-aminoantipyrine, an active dipyrone metabolite, described as an antioxidant and anti-inflammatory agent; and the pharmacophore fragment 1,4-dioxo-2-butenyl, a cytotoxic agent. The results indicated that IR-01 is an effective chemoprotector because it can prevent clastogenic and/or aneugenic damage, has good potential to prevent genomic damage, can increase splenic phagocytosis and lymphocyte frequency and induces cell death. However, its use as an adjuvant in combination with chemotherapy is discouraged since IR-01 interferes in the effectiveness of the tested chemotherapeutic agents. This is a pioneer study as it demonstrates the chemopreventive effects of IR-01, which may be associated with the higher antioxidant activity of the precursor structure of 4-aminoantipyrine over the effects of the 1,4-dioxo-2-butenyl fragment |
Disciplinas: | Medicina, Química, Biología |
Palabras clave: | Terapéutica y rehabilitación, Química farmacéutica, Biología celular, Fagocitosis esplénica, Ensayo cometa, Prueba de micronúcleos, Muerte celular, Quimioprevención |
Keyword: | Therapeutics and rehabilitation, Medicinal chemistry, Cell biology, Splenic phagocytosis, Comet assay, Micronucleus test, Cell death, Chemoprevention |
Texto completo: | Texto completo (Ver PDF) |