New series of monoamidoxime derivatives displaying versatile antiparasitic activity

Abstract

Following the promising antileishmanial results previously obtained in monoamidoxime series, a new series of derivatives was synthesized using manganese(III) acetate, Wittig reactions and Suzuki–Miyaura cross coupling reactions. Pharmacomodulation in R1, R2 or R3 substituents on the amidoxime structure is shown to influence antiprotozoan activity in vitro: a monosubstituted phenyl group in R1 (32–35) led to an activity against Leishmania donovani promastigotes (32, IC50 = 9.16 μM), whereas a polysubstituted group (36–37) led to an activity against Plasmodium falciparum (36, IC50 = 2.76 μM). Modulating chemical substituents in R2 and R3 only influenced the antiplasmodial activity in vitro. This suggests that the amidoxime scaffold has properties that could make it a promising new antiparasitic pharmacophore.