β′-Hydroxy-α,β-unsaturated ketones: A new pharmacophore for the design of anticancer drugs. Part 2.†

Novel antiproliferative β'-acyloxy-α,β-unsaturated ketones were obtained by means of an iron(III)-catalyzed multicomponent domino process (ABB' 3CR). The most active derivatives displayed Gl 50 values in the range of 0.5-3.9 μM against a panel of representative human solid tumor cell lines: A2780, SW1573, HBL-100, T-47D and WiDr. Analysis of cells following 24 h exposure to these drugs showed cell cycle arrest in the S and G 2/ M phase, in a dose-dependent manner. Our data indicate that the β'-acyloxy-α,β-unsaturated ketones cause permanent damage to the cells and induce apoptosis.