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. Epub 2014 Oct 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / chemical synthesis
  • 4-Butyrolactone / chemistry
  • 4-Butyrolactone / pharmacology
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • methyl 3-(4-methoxybenzyl)-2-methyl-5-oxo-2-phenyltetrahydrofuran-3-carboxylate
  • 4-Butyrolactone