Influence of the skeleton on the cytotoxicity of flavonoids

Analogs of 3′-amino-5-hydroxy-3,6,7,8,4′-pentamethoxy-flavone, a strongly cytotoxic and antimitotic semisynthetic flavone, were synthesized in the aurone, isoflavone and isoflavanone series. Comparison of the biological activity of these new compounds with the reference showed a potent cytotoxicity only in the flavone series. Influence of the hydroxy group (at C-5 in flavones, at C-4 in aurones) on the cytotoxicity, known to be favorable in flavones, was found to be detrimental in aurones. This observation was related to the hydrogen bonding formed with the carbonyl group, strong in the flavones, but of weak intensity in the aurones.

Aurone, isoflavone and isoflavanone analogs of the cytotoxic flavone 1 were synthesized. Cytotoxicity of these new compounds (and fifteen other ones) was evaluated, and SARs discussed.Figure optionsDownload as PowerPoint slide