2-Arylpaullones are selective antitrypanosomal agents.

Abstract Antileishmanial paullone–chalcone hybrid molecules display antiparasitic activity against Trypanosoma brucei rhodesiense blood stream forms, albeit with low selectivity against human THP-1 cells. In order to develop less toxic analogues, paullones with acrylamide or aryl substituents in 2-position were synthesized, of which the latter exhibited potent antiparasitic activity with excellent selectivity profiles. The most potent compound identified in this study was 9- tert -butyl-2-(4-morpholinophenyl)paullone ( 3i ) which inhibited the parasites at submicromolar concentrations (GI 50  = 510 nM) with a selectivity index of 157.