Synthesis and antileishmanial activity of styrylquinoline-type compounds: in vitro and in vivo studies

In this research, four styrylquinolines were synthesized and evaluated in vitro and in vivo antileishmanial activity. The following compounds were obtained: 2-[(E)-2-(2-chlorophenyl)ethenyl]quinoline-8-ol (3a), 4-bromo-2-[(E)-2-(8-hydroxyquinoline-2-yl)ethenyl]phenyl-acetate (3b), 4-[(E)-2-(8-hydroxyquinoline -2-yl)ethenyl]-2,6- dimethoxyphenyl acetate (3c), 2-{(E)-2-[2-(acetyloxy)-5-nitrophenyl]ethenyl} quinoline-8-yl-acetate (3d). Of the four compounds, evaluated in vitro, 3b and 3c were active against intracellular amastigotes at median effective concentrations (EC₅₀) of 2.8 and 3.14 μg mL^-1 and exhibited toxicity over human U-937 macrophages at median lethal concentrations (LC₅₀) of 5.5 and 3.4 μg mL^-1, which showed selectivity indices (SI) of 1.96 and 1.08. The results of in vivo studies of therapeutic response in hamsters with experimental CL caused by L. (V) panamensis indicated that with topical creams at 2% of compounds 3b and 3c produced a clinical improvement of 4/5 (80%) of hamsters with 3b, and with 3c a complete cure of 1/5 (20%) and a clinical improvement of 2/5 (40%) of the hamsters, while the in vivo control drug (MA-il) produced clinical improvement in 3/5 (60%) of hamsters.