title: Synthesis of 2,3-di- and 2,2,3-trisubstituted-3-methoxycarbonyl-γ-butyrolactones as potent antitumor agents.
abstract: Various 2,3-substituted γ-butyrolactones have been synthesized by three-component reaction of aryl bromides, dimethyl itaconate and carbonyl compounds. The in vitro cytotoxic activity of these products was evaluated against a representative panel of cancer cell lines (KB, HCT116, MCF7, MCF7R, PC3, SK-OV3, HL60 and HL60R). One compound (4x) displays a good anti-proliferative activity with IC50 in the sub-micromolar range. The mechanism of action has been investigated using flow cytometry.
authors.affiliation: Électrochimie et Synthèse Organique, Institut de Chimie et des Matériaux Paris-Est, UMR 7182 CNRS - Université Paris-Est Créteil, 2-8 rue Henri Dunant, 94320 Thiais, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Le Floch
authors.affiliation: Électrochimie et Synthèse Organique, Institut de Chimie et des Matériaux Paris-Est, UMR 7182 CNRS - Université Paris-Est Créteil, 2-8 rue Henri Dunant, 94320 Thiais, France. Electronic address: legall@icmpe.cnrs.fr.
authors.forename: Erwan
authors.initials: E
authors.lastname: Le Gall
authors.affiliation: Électrochimie et Synthèse Organique, Institut de Chimie et des Matériaux Paris-Est, UMR 7182 CNRS - Université Paris-Est Créteil, 2-8 rue Henri Dunant, 94320 Thiais, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Sengmany
authors.affiliation: Plateforme Chromatographie Analytique et Préparative, Institut de Chimie et des Matériaux Paris-Est, UMR 7182 CNRS - UniversitéParis-Est Créteil, 2-8 rue Henri Dunant, 94320 Thiais, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Renevret
authors.affiliation: Électrochimie et Synthèse Organique, Institut de Chimie et des Matériaux Paris-Est, UMR 7182 CNRS - Université Paris-Est Créteil, 2-8 rue Henri Dunant, 94320 Thiais, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Léonel
authors.affiliation: Électrochimie et Synthèse Organique, Institut de Chimie et des Matériaux Paris-Est, UMR 7182 CNRS - Université Paris-Est Créteil, 2-8 rue Henri Dunant, 94320 Thiais, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Martens
authors.affiliation: Ciblothèque cellulaire, Institut de Chimie des Substances Naturelles, CNRS-UPR 2301, Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Cresteil
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; C000600801:methyl 3-(4-methoxybenzyl)-2-methyl-5-oxo-2-phenyltetrahydrofuran-3-carboxylate; D015107:4-Butyrolactone
keywords: Biological evaluation; Cytotoxic activity; Lactones; Multicomponent reaction; Paraconic acid analogs