Synthesis, evaluation against Leishmania amazonensis and cytotoxicity assays in macrophages of sixteen new congeners Morita-Baylis-Hillman adducts

Abstract

We report the design, synthesis, in vitro evaluation against Leishmania amazonensis (IC(50)), cytotoxicity assays in macrophages (CC(50)), and selectivity index (SICC(50)/IC(50)) of sixteen new congeners aromatic Morita-Baylis-Hillman adducts 1-16. The 1-16 were prepared in good to excellent yields (58%-97%) from the "one pot" Morita-Baylis-Hillman Reaction between the aldehydes 29-36 and the acrylates 27 or 28 under DABCO as promoter. The MBHA 2-[Hydroxy(2-nitrophenyl)propyl] propanoate (1, IC(50) = 7.52 μg/mL or 28.38 μM; CC(50) = 35.77 μg/mL or 134.98 μM; SI = 4.75) and 2-[Hydroxy(2-nitrophenyl)hydroxyethyl] propanoate (9, IC(50) = 5.48 μg/mL or 20.52 μM; CC(50) = 29.81 μg/mL or 111.64c μM and, SI = 5.43) were the most effective and safe evaluated compounds.