Synthesis of novel α-santonin derivatives as potential cytotoxic agents

Ten novel α-santonin derivatives have been synthesized as cytotoxic agents. The in vitro antitumor activity of these compounds has been evaluated against cancer cells lines. Structure-activity relationships indicate that α-methylene-γ-lactone and endoperoxide functionalities play important roles in conferring cytotoxicity. The compounds 2–4, possessing the α-methylene-γ-lactone group showed IC50 values between 5.70 and 16.40 μM. Mixture of isomers 5 and 6, with the α-methylene-γ-lactone and endoperoxide functionalities, displayed the greatest activity, with IC50 values between 1.45 and 4.35 μM. The biological assays conducted with normal cells revealed that the compounds 2, 5 and 6 are selective against cancer cells lines tested. Bioactive lactones described herein and in our previous report did not cause disruption of the cell membrane in mouse erythrocytes.

Several α-santonin lactones derivatives were synthesized in moderate to high yields and found to display cytotoxicity against cancer cell lines. α-methylene-γ-lactone and endoperoxide bridge functionalities play important roles in conferring cytotoxic activity.Figure optionsDownload as PowerPoint slideResearch highlights
► Sesquiterpene lactones with improved anti-cancer activity.
► Alpha-santonin derivatives as cytotoxic agents.
► Cytotoxicity of Alpha-santonin derivatives.
► First total synthesis of the natural product Parishin A.
► Conversion of alpha-santonin into Parishin A via a photochemical reaction.