New series of monoamidoxime derivatives displaying versatile antiparasitic activity

• DOI: 10.1016/j.ejmech.2014.07.113
• Publication Date: 2014-09-30T17:31:21Z
• Authors: Clémence Tabélé; Anita Cohen; Christophe Curti; Ahlem Bouhlel; Sébastien Hutter; Vincent Remusat; Nicolas Primas; Thierry Terme; Nadine Azas; Patrice Vanelle
• Keywords: Spectrometry, Mass, Electrospray Ionization; Antiparasitic Agents; [CHIM.ORGA]Chemical Sciences/Organic chemistry; [CHIM.THER] Chemical Sciences/Medicinal Chemistry; Manganese(III) acetate; [CHIM.THER]Chemical Sciences/Medicinal Chemistry; [CHIM.ORGA] Chemical Sciences/Organic chemistry; 01 natural sciences; Amidoximes; 0104 chemical sciences; 3. Good health; Inhibitory Concentration 50; Dihydrofuran; Oximes; Pharmacomodulation; Antiprotozoan activity in vitro; Carbon-13 Magnetic Resonance Spectroscopy; Palladium-catalyzed coupling reactions; Cytotoxicity in vitro

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 R(1), R(2) or R(3) 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 R(2) and R(3) only influenced the antiplasmodial activity in vitro. This suggests that the amidoxime scaffold has properties that could make it a promising new antiparasitic pharmacophore.