Zhi Chen, Shi-Chao Chen, Bo Li, Yong-An Yang and Jing Zhang* Pages 715 - 723 ( 9 )
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.
Glycyrrhetic acid, natural product, anti-inflammatory activity, structure-activity relationship, molecular hybridization, X-ray crystallography.
Anqing Medical and Pharmaceutical College, Anqing 246052, Elion Nature Biological Technology Co., Ltd, Nanjing 210038, Anhui Prevention and Treatment Center for Occupational Disease, Anhui No. 2 Provincial People's Hospital, Hefei 230032, Elion Nature Biological Technology Co., Ltd, Nanjing 210038, Anhui Prevention and Treatment Center for Occupational Disease, Anhui No. 2 Provincial People's Hospital, Hefei 230032