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Despite advances in ovarian cancer treatment, the five-year overall survival rate is less than 30% with the presence of cancer stem cells (CSCs). To develop CSC-targeting therapy, a series of 18β-glycyrrhetinic acid (GA) derivatives containing cinnamamide moiety have been designed, synthesized, and screened for their antiproliferative activity in SKOV3 and OVCAR3 cells. Most of the compounds exhibited stronger antiproliferative activity than GA, and compound 7c was the most active one. Further biological studies showed that compound 7c could induce apoptosis and suppress migration. In addition, compound 7c could not only observably decrease the colony formation and sphere formation ability, but also significantly reduce the CD44 + , CD133 + , and ALDH + subpopulation in SKOV3 and OVCAR3 cells. In conclusion, these results indicate that compound 7c is a promising anti-CSC agent for further anti-ovarian cancer studies.

Synthesis and discovery of 18β-glycyrrhetinic acid derivatives inhibiting cancer stem cell properties in ovarian cancer cells