Background: Inflammation is a biological response of body tissues to harmful stimuli,
so it is desirable to search for novel anti-inflammatory agents with improved pharmaceutical profiles
and reduced adverse effects.
Objective: This study was to explore natural anti-inflammatory agents and improve therapeutic application
of glycyrrhetic acid (GA) through molecular hybridization with active aromatics.
Methods: Fourteen novel GA-aromatic hybrids were synthesized and evaluated for their antiinflammatory
activities by inhibiting LPS-induced nitric oxide (NO) release in RAW264.7 cells.
The synthesized compounds were characterized by single-crystal X-ray diffraction, 1H NMR, 13C
NMR and HRMS.
Results: The structure-activity relationship (SAR) study indicated that compounds with styryl displayed
better NO inhibitory activity. Among them, compounds 2a and 3c exhibited the most promising
activity with IC50 values of 9.93 μM and 12.25 μM, respectively. In addition, X-ray singlecrystal
diffraction data for compounds 2e and 3c showed that the absolute configuration of GA
skeleton was consistent with that of natural 18 β-glycyrrhetic acid.
Conclusion: The results showed that GA-aromatic hybrids were a new class of anti-inflammatory
agents and this study provided useful information on further optimization.