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

We report the design, synthesis, in vitro evaluation against Leishmania amazonensis (IC50), cytotoxicity assays in macrophages (CC50), and selectivity index (SI=-CC50/IC50) 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, IC50 = 7.52 mu g/mL or 28.38 mu M; CC50 = 35.77 mu g/mL or 134.98 mu M; SI = 4.75) and 2-[Hydroxy(2-[nitrophenyl)hydroxyethyl] propanoate (9, IC50 = 5.48 mu g/mL or 20.52 mu M; CC50 = 29.81 mu g/mL or 111.64c mu M and, SI = 5.43) were the most effective and safe evaluated compounds. (C) 2011 Elsevier Masson SAS. All rights reserved.