Antiproliferative Activity and Target Analysis of 18β-Glycyrrhetinic Acid Derivatives Modified With α, β-Unsaturated Carbonyl Groups.

Cancer is one of the most complex diseases. Its multidrug resistance and poor prognosis make the development of antitumor drugs still a difficult task. 18β-glycyrrhetinic acid (18β-GA) has shown great potential for tumor prevention and treatment. However, inherent defects, such as low bioavailability, limit its use. Herein, based on a molecular hybridization strategy, two series of α, β-unsaturated carbonyl modified 18β-GA derivatives were synthesized using 18β-GA as the parent nucleus. Among them, compounds 9a, 9g and 9i exhibited the strongest antiproliferative activity, with IC50 values ranging from 1.52 to 3.46 μM against HCT-116, SH-SY5Y and HepG2 cells. The key target of the three active derivatives was predicted to be human STAT3 through reverse target finding. Docking analysis proved that all three derivatives showed strong binding affinity to STAT3 in silico, suggesting potential as STAT3 inhibitors.