title: Uncovering new structural insights for antimalarial activity from cost-effective aculeatin-like derivatives.
abstract: A series of new aculeatin-like analogues were synthesized in two steps by combining two sets of building blocks. Many compounds showed inhibitory activities in vitro against Plasmodium falciparum and have helped to gain more insight into structure-activity relationships around the spirocyclohexadienone pharmacophoric scaffold. Plasmodium falciparum thioredoxin reductase (PfTrxR) has been investigated as a putative cellular target. Moreover, a new aculeatin-like scaffold without Michael acceptor properties, efficient at 0.86 μM against P. falciparum 3D7, was identified and raises the prospect of developing a new antimalarial agent.
authors.affiliation: Département de Pharmacochimie Moléculaire, Univ. Grenoble-Alpes, CNRS UMR 5063, CNRS ICMG FR 2607, bâtiment André Rassat, 470 rue de la Chimie, F-38041 Grenoble Cedex 9, France. yung-sing.wong@ujf-grenoble.fr.
authors.forename: Matthias
authors.initials: M
authors.lastname: Winkler
authors.forename: Marjorie
authors.initials: M
authors.lastname: Maynadier
authors.forename: Sharon
authors.initials: S
authors.lastname: Wein
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Lespinasse
authors.forename: Giovanna
authors.initials: G
authors.lastname: Boumis
authors.forename: Adriana E
authors.initials: AE
authors.lastname: Miele
authors.forename: Henri
authors.initials: H
authors.lastname: Vial
authors.forename: Yung-Sing
authors.initials: YS
authors.lastname: Wong
mesh_terms: D000962:Antimalarials / Q000737:chemistry / Q000191:economics* / Q000494:pharmacology*; D003512:Cyclohexanones / Q000737:chemistry / Q000191:economics* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D013141:Spiro Compounds / Q000737:chemistry / Q000191:economics* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D003512:Cyclohexanones; D013141:Spiro Compounds; C476177:aculeatin A