title: 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 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.
authors.affiliation: Aix-Marseille Université, CNRS, ICR, UMR 7273, Laboratoire de Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin, CS30064, 13385 Marseille Cedex 05, France.
authors.forename: Clémence
authors.initials: C
authors.lastname: Tabélé
authors.affiliation: Aix-Marseille Université, IRD, IRBA, Université de Montpellier 1, IP-TPT UMR_MD 3, Infections Parasitaires, Transmission, Pharmacologie et Thérapeutique, Faculté de Pharmacie, 27 Boulevard Jean Moulin, CS30064, 13385 Marseille Cedex 05, France.
authors.forename: Anita
authors.initials: A
authors.lastname: Cohen
authors.affiliation: Aix-Marseille Université, CNRS, ICR, UMR 7273, Laboratoire de Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin, CS30064, 13385 Marseille Cedex 05, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Curti
authors.affiliation: Aix-Marseille Université, CNRS, ICR, UMR 7273, Laboratoire de Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin, CS30064, 13385 Marseille Cedex 05, France.
authors.forename: Ahlem
authors.initials: A
authors.lastname: Bouhlel
authors.affiliation: Aix-Marseille Université, IRD, IRBA, Université de Montpellier 1, IP-TPT UMR_MD 3, Infections Parasitaires, Transmission, Pharmacologie et Thérapeutique, Faculté de Pharmacie, 27 Boulevard Jean Moulin, CS30064, 13385 Marseille Cedex 05, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Hutter
authors.affiliation: Aix-Marseille Université, CNRS, ICR, UMR 7273, Laboratoire de Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin, CS30064, 13385 Marseille Cedex 05, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Remusat
authors.affiliation: Aix-Marseille Université, CNRS, ICR, UMR 7273, Laboratoire de Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin, CS30064, 13385 Marseille Cedex 05, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Primas
authors.affiliation: Aix-Marseille Université, CNRS, ICR, UMR 7273, Laboratoire de Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin, CS30064, 13385 Marseille Cedex 05, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Terme
authors.affiliation: Aix-Marseille Université, IRD, IRBA, Université de Montpellier 1, IP-TPT UMR_MD 3, Infections Parasitaires, Transmission, Pharmacologie et Thérapeutique, Faculté de Pharmacie, 27 Boulevard Jean Moulin, CS30064, 13385 Marseille Cedex 05, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Azas
authors.affiliation: Aix-Marseille Université, CNRS, ICR, UMR 7273, Laboratoire de Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin, CS30064, 13385 Marseille Cedex 05, France. Electronic address: patrice.vanelle@univ-amu.fr.
authors.forename: Patrice
authors.initials: P
authors.lastname: Vanelle
mesh_terms: D000977:Antiparasitic Agents / Q000737:chemistry* / Q000494:pharmacology*; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D020128:Inhibitory Concentration 50; D010091:Oximes / Q000737:chemistry* / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000977:Antiparasitic Agents; D010091:Oximes; C070491:Amidox
keywords: Amidoximes; Antiprotozoan activity in vitro; Cytotoxicity in vitro; Dihydrofuran; Manganese(III) acetate; Palladium-catalyzed coupling reactions; Pharmacomodulation