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 (SICC50/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 μg/mL or 28.38 μM; CC50 = 35.77 μg/mL or 134.98 μM; SI = 4.75) and 2-[Hydroxy(2-nitrophenyl)hydroxyethyl] propanoate (9, IC50 = 5.48 μg/mL or 20.52 μM; CC50 = 29.81 μg/mL or 111.64c μM and, SI = 5.43) were the most effective and safe evaluated compounds.

The “one pot” synthesis (58%–97%) of sixteen new Morita–Baylis–Hillman adducts 1–16 was presented. All compounds were screened against Leishmania amazonensis (IC50), cytotoxicities assay in macrophages (CC50), and the Selectivity Index (SI = IC50/CC50) were calculated for this new promising class of anti-parasitic compounds.Figure optionsDownload as PowerPoint slideHighlights
► Aromatic Morita–Baylis–Hillman adducts (MBHA) were active compounds against the Leishmania amazonensis.
► We used the classic bioisosterism strategy for molecular modification, to idealize the new congeners MBHA.
► All new adducts were very active against L. amazonensis and the most of the selectivity indexes (SI) were greater than 1.