Discovery of an indole-substituted furanone with tubulin polymerization inhibition activity

Analogs of diarylpyrrolinone lead compound 1 were prepared and tested for anti-proliferative activity in U-937 cancer cells. Alterations of 1 focused on modifying the two nitrogen atoms: a) the pyrrolinone nitrogen atom was substituted with a propyl group or replaced with an oxygen atom (furanone), and b) the substituents on the indole nitrogen were varied. These changes led to the discovery of a furanone analog 3b with sub-micromolar anti-cancer potency and tubulin polymerization inhibition activity.

Automated summary

By altering the structure of the lead compound, analogs were synthesized and tested for anti-proliferative activity in cancer cells. A furanone analog 3b was discovered with potent anti-cancer activity and tubulin polymerization inhibition activity, showing the potential for further development in cancer therapy.