title: 2-Aryl-3H-indol-3-ones: synthesis, electrochemical behaviour and antiplasmodial activities.
abstract: The synthesis of indolone derivatives and their antiplasmodial activity in vitro against Plasmodium falciparum at the blood stage are described. The 2-aryl-3H-indol-3-ones were synthesized via deoxygenation of indolone-N-oxides. Electrochemical behaviour, antiplasmodial activity and cytotoxicity on human tumor cell lines were compared to those of indolone-N-oxides. The antiplasmodial IC50 (concentrations at 50% inhibition) of these compounds ranged between 49 and 1327 nM. Among them, the 2-(4-dimethylaminophenyl)-5-methoxy-indol-3-one, 7, had the best antiplasmodial activity in vitro (IC50 = 49 nM; FcB1 strain) and selectivity index (SI (CC50 MCF7/IC50 FcB1) = 423.4). Thus, the hits identified in this deoxygenated series correspond to their structural homologs in the N-oxide series with comparable electrochemical behaviour at the nitrogen-carbon double bond.
authors.affiliation: Université de Toulouse III, UPS, PHARMA-DEV, UMR 152, 118 Route de Narbonne, F-31062 Toulouse Cedex 9, France; IRD, UMR 152, F-31062 Toulouse Cedex 9, France. Electronic address: ennaji.najahi@univ-tlse3.fr.
authors.forename: Ennaji
authors.initials: E
authors.lastname: Najahi
authors.affiliation: Université de Toulouse III, UPS, PHARMA-DEV, UMR 152, 118 Route de Narbonne, F-31062 Toulouse Cedex 9, France; IRD, UMR 152, F-31062 Toulouse Cedex 9, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Valentin
authors.affiliation: Université de Toulouse III, UPS, PHARMA-DEV, UMR 152, 118 Route de Narbonne, F-31062 Toulouse Cedex 9, France; IRD, UMR 152, F-31062 Toulouse Cedex 9, France.
authors.forename: Paul-Louis
authors.initials: PL
authors.lastname: Fabre
authors.affiliation: Université de Toulouse III, UPS, PHARMA-DEV, UMR 152, 118 Route de Narbonne, F-31062 Toulouse Cedex 9, France; IRD, UMR 152, F-31062 Toulouse Cedex 9, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Reybier
authors.affiliation: Université de Toulouse III, UPS, PHARMA-DEV, UMR 152, 118 Route de Narbonne, F-31062 Toulouse Cedex 9, France; IRD, UMR 152, F-31062 Toulouse Cedex 9, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Nepveu
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D055664:Electrochemical Techniques; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D061986:MCF-7 Cells; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D000970:Antineoplastic Agents; D007211:Indoles
keywords: 2-Aryl-3H-indol-3-ones; Antiplasmodial activity; Deoxygenation; Electrochemical behaviour; Indolone-N-oxides