Detalle Publicación

ARTÍCULO
A step towards development of promising trypanocidal agents: synthesis, characterization and in vitro biological evaluation of ferrocenyl Mannich base-type derivatives
Autores: Paucar Bernabé, Rocio Valeria; Martin-Escolano, R.; Moreno de Viguri, Elsa; Cirauqui, N. ; Rodrigues, C. R.; Marin, C. ; Sanchez-Moreno, M. ; Pérez Silanes, Silvia; Ravera, M.; Gabano, E. (Autor de correspondencia)
Título de la revista: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
ISSN: 0223-5234
Volumen: 163
Páginas: 569 - 582
Fecha de publicación: 2019
Lugar: WOS
Resumen:
Chagas disease is a neglected chronical parasitosis caused by the parasite Trypanosoma cruzi (T. cruzi). Nine ferrocenyl Mannich base derivatives were synthetized and characterized to explore their in vitro activity on three T. cruzi strains of the parasite and their cytotoxicity on Vero cells to calculate the selectivity index (SI). Compound 2, 1-ferrocenyl-3-(4-(4-(trifluoromethyl)phenyl)piperazin-1-yl)propan-1-one, stood out as the most promising derivative showing a half maximal inhibitory concentration (IC50) value around 5 mu M in both amastigote and trypomastigote forms of T. cruzi and SI values higher than 13, being the best value on the trypomastigote forms of the Arequipa strain (SI = 41.7). Moreover, 2 decreased the number of infected cells and was not genotoxic. Furthermore, its possible mechanism of action was studied through the alteration of the metabolites excreted by the parasite during glucose metabolism, the detection of mitochondrial alterations and the inhibition of superoxide dismutase (SOD). Finally, docking studies were executed to analyze the binding mode of the studied compounds to Fe-SOD enzyme.