Novel Linezolid Analogues with Antiparasitic Activity against Hymenolepis nana

Abstract The stereoselective synthesis and anti- Hymenolepis nana activity of six Linezolid-type compounds, obtained by chemical modification of L-Alanine, are reported in this work. The synthetic strategy was to prepare diasteromeric N,N-dibenzylamino oxazolidinones 1 and 2, and coupling with 4-(4-bromophenyl)morpholine (3) to obtain N,N-dibenzylamino Linezolid analogues 4 and 5. A hydrogenolysis reaction over 4 and 5 resulted in amino-free Linezolid analogues 6 and 7, which were acetylated to reach diasteromeric Linezolid analogues 8 and 9. The six Linezolid analogues 4-9 show in vitro antiparasitic activity against Hymenolepis nana cestode, but not against several bacterial strains. Interestingly, compounds 6, 7 and 9 exhibit high potency, having shorter paralysis and death times after exposure (6 to 10 and 18 to 21 min, respectively), shorter than those found with antihelmintic compound Praziquantel (20 and 30 min) at 20 mg/mL. In addition, a cytocompatibility assay of 6-9 with human cells (ARPE-19 cells) demonstrate a non-cytotoxic effect at 0.4 mM. These results show the pharmacological potential of the newly reported Linezolid-type analogues as antiparasitic agents against Hymenolepis nana.