2. Academic Validation
  3. Synthesis of 2,3-di- and 2,2,3-trisubstituted-3-methoxycarbonyl-γ-butyrolactones as potent antitumor agents

Synthesis of 2,3-di- and 2,2,3-trisubstituted-3-methoxycarbonyl-γ-butyrolactones as potent antitumor agents

  • Eur J Med Chem. 2015 Jan 7;89:654-70. doi: 10.1016/j.ejmech.2014.10.074.
Camille Le Floch 1,  Erwan Le Gall 2,  Stéphane Sengmany 1,  Patrice Renevret 3,  Eric Léonel 1,  Thierry Martens 1,  Thierry Cresteil 4
Affiliations

Affiliations

  • 1 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.
  • 2 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: [email protected].
  • 3 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.
  • 4 Ciblothèque cellulaire, Institut de Chimie des Substances Naturelles, CNRS-UPR 2301, Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France.
PMID: 25462273 DOI: 10.1016/j.ejmech.2014.10.074
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.

Keywords

Biological evaluation; Cytotoxic activity; Lactones; Multicomponent reaction; Paraconic acid analogs.

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