Browsing by Author "Fonseca Berzal, Cristina"

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    In vitro phenotypic screening of 7-chloro-4-amino(oxy)quinoline derivatives as putative anti-Trypanosoma cruzi agents
    (2014) Kouznetsov, Vladimir V.; Gómez Barrio, Alicia; Escario, José A.; Rojas Ruiz, Fernando A.; Fonseca Berzal, Cristina
    In this study, a series of 22 pre-synthesized 7-chloro-4-mino(oxy)quinoline derivatives was assayed in vitro as potential antichagasic agents. A primary screening against Trypanosoma cruzi epimastigotes and a non-specific cytotoxicity assay on murine fibroblasts were simultaneously performed, resulting quinolines 3, 7 and 12 with great selectivity (SI) on the extracellular parasite (SI7, SI3 , SI12 and SIBZ >9.44). Therefore, the activity of these derivatives was evaluated on intracellular amastigotes, achieving derivative 7 the best SI (SI = 12.73). These results, supported by the in silico prediction of a good oral bioavailability and a suitable risk profile, propose the 4-amino-7-chloroquinoline scaffold as a potential template for designing trypanocidal prototypes.
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    Selective activity of 2,4-diaryl-1,2,3,4-tetrahydroquinolines on Trypanosoma cruzi epimastigotes and amastigotes expressing β-galactosidase
    (2013-07) Fonseca Berzal, Cristina; Merchan Arenas, Diego Rolando; Romero Bohórquez, Arnold R.; Escario, José A.; Kouznetsov, Vladimir V.; Gómez Barrio, Alicia
    The growth inhibitory effect on Trypanosoma cruzi epimastigotes and the unspecific cytotoxicity over NCTC-929 fibroblasts of two series of previously synthesized 2,4-diaryl-1,2,3,4-tetrahydroquinolines (THQ), have been studied in vitro and compared with those of benznidazole (BZ). Derivatives AR39, AR40, AR41, AR91 and DM15 achieved outstanding selectivity indexes (SI) on the extracellular form (SITHQ > SIBZ > 9.44) and thus, were tested in a more specific in vitro assay against amastigotes, showing less effectiveness than the reference drug (SIBZ > 320) but also accomplishing great selectivity on the intracellular stage (SITHQ > 25). These promising results, supported by the in-silico prediction of high bioavailability and less potential risk than benznidazole, reveal several tetrahydroquinolines as prototypes of potential antichagasic drugs.