In this study, we report the synthesis and evaluation of in vitro and in vivo antitrypanosomal activity of styrylquinoline-like compounds (SQ) 3a-h . Synthesis was carried out by using quinaldine and 8- hydroxyquinaldine with a variety of aromatic aldehydes. The structure of SQs was corroborated by one and two-dimension NMR spectroscopy. In vitro antitrypanosomal activity on T. cruzi Talahuen strain was evaluated using β-galactosidase enzymatic method; cytotoxicity on U-937 cells was assessed by using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] method. On the other hand, in vivo therapeutical response to 3a-f compounds was evaluated in BALB/c mice ( Mus musculus ) experimentally infected with T. cruzi blood trypomastigotes and then orally administered with 100 mg/kg weight day for 20 days. All of the compounds showed in vitro activity with EC 50 values ranging between 4.6 ± 0.1 μg/mL (14.4 μM) and 36.6 ± 6.1 μg/mL (91 μM). Furthermore, treatment with 3a-f compounds for 20 days resulted in improvement in all of the mice, with a 83–96% decrease in parasitic load at day 90 post-treatment. Treatment with benznidazol (BZ) managed to cure 100% of the mice at the end of treatment. None of the treatments affected the weight of the animals or alanine aminotransferase (ALT), blood urea nitrogen (BUN) and creatinine levels in serum. These results suggest a therapeutic potential of 3a-f compounds as treatment for the infection.
ResumenEl presente estudio reporta la síntesis de cinco (E)-estirilquinolinas (Q.1, Q.2, Q.3, Q.5, Q.6) y tres derivados O-alquilados (Q.1a, Q.6a, Q.6b) y la evaluación de su actividad antimalárica y citotóxica in vitro. Para obtener las estirilquinolinas se empleó la reacción de condensación tipo Perkin a partir de 8-hidroxiquinaldina con aldehídos aromáticos. La actividad antimalárica se realizó empleando el método Radioisotópico con cepas FCB-2 de Plasmodium falciparum (resistente a la cloroquina) y para la actividad citotóxica se empleó el método del MTT con células HepG2. La mayoría de los compuestos mostraron ser activos antimaláricos. Los que presentan mayor actividad son el Q.3 (IC50 6.4µM), y el Q.5 (IC5010.8 µM) aunque todos mostraron ser citotóxicos a concentraciones superiores a 1µg/mL. Las estructuras de estos compuestos se confirmaron empleando técnicas espectroscópicas de Infrarrojo y Resonancia Magnética Nuclear en una y dos dimensiones. Palabras clave: estirilquinolinas, actividad antimalárica, reacción de Perkin, compuestos o-alquilados, citotoxicidad Evaluation of Antimalarial and Cytotoxic Activity of Styrylquinolines obtained from 8-Hydroxyquinaldine with Aromatic Aldehydes AbstractThis study reports the synthesis of five (E)-Styrylquinolines (Q.1, Q.2, Q.3, Q.5, Q.6) and three O-alkylated derivatives (Q.1a, Q.6a, Q 6 b) and the evaluation of its antimalarial activity and cytotoxic in vitro. For Styrylquinolines Perkin condensation reaction type from 8-hydroxyquinaldine with aromatic aldehydes was used. Antimalarial activity was performed using the method Radioisotope with FCB-2 strains of Plasmodium falciparum (chloroquine-resistant) and for the cytotoxic activity the MTT method with HepG2 cells was employed. Most compounds showed to be active antimalarial. Those with higher activity were Q.3 (IC50 6.4μM) and Q.5 (IC5010.8 µM), although all of them were cytotoxic at concentrations above 1 µg / mL. The structures of these compounds were confirmed using infrared spectroscopy techniques and MRI in one and two dimensions.
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