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.

背景：炎症是人体组织对有害刺激物的生物反应，因此，人们希望寻找具有改善药物特性和减少不良反应的新型抗炎药。

目的：本研究旨在探索天然抗炎药，并通过与活性芳香剂的分子杂交来改善甘草次酸（GA）的治疗应用。

方法：合成了14种新颖的GA-芳香族杂种，并通过抑制LPS诱导的RAW264.7细胞中一氧化氮（NO）释放来评估其抗炎活性。通过单晶X射线衍射，1 H NMR，13 C NMR和HRMS对合成的化合物进行表征。

结果：结构-活性关系（SAR）研究表明，带有苯乙烯基的化合物显示出更好的NO抑制活性。其中，化合物2a和3c表现出最有希望的活性，IC50值分别为9.93μM和12.25μM。另外，化合物2e和3c的X射线单晶衍射数据表明，GA骨架的绝对构型与天然的18β-甘草次酸的构型是一致的。

结论：结果表明，GA-芳香族杂种是一类新型的抗炎药，这项研究为进一步优化提供了有用的信息。