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.