目的设计合成一系列黄酮醇类衍生物,并评价其抗神经炎症活性。方法以间苯三酚为原料,经傅克酰基化、缩合、Algar-Flynn-Oyamada和Claisen重排等反应合成目标化合物。采用CCK-8法检测化合物对小鼠小胶质细胞(BV2细胞)的无毒剂量范围。应用脂多糖(LPS)和干扰素γ(IFN-γ)与BV2细胞孵育24 h建立神经炎症细胞模型,用Griess法检测BV2细胞释放的一氧化氮(NO)含量。结果合成了8个黄酮醇类化合物,其中4个具有异戊烯基,目标化合物的结构经质谱、核磁共振氢谱确定。化合物6a~6d和10a~10d在1~100μmol·L-1的剂量范围内均未显示细胞毒性。化合物6a和10a(10μmol·L-1)与BV2细胞预孵育24 h能够明显抑制LPS/IFN-γ诱导的炎性介质NO过度产生和释放。结论合成的黄酮醇类化合物6a和10a具有抗神经炎症的活性。
A series of flavonols were designed,synthesized and the target compounds were obtained from phloroglucinol via Friedel-Crafts acylation,condensation,Algar-Flynn-Oyamada and the Claisen rearrangement reactions.Their structures were confirmed by M S and1H-NM R.The non-cytotoxicity synthesized compounds on cultured BV2 cells(mouse microglial cells) were measured by using CCK-8 assay,and none showed any cytotoxicity in BV2 cells at the dose of 1-100 μmol·L-1.The cellular model of neuroinflmmation was established by incubation of BV2 cells with lipopolysaccharide(LPS) and interferon γ(IFN-γ) for24 h,and the release of nitric oxide(NO) from BV2 cells was detected by using Griess assay.Preincubation of BV2 cells with compounds 6a and 10a(10 μmol·L-1) for 24 h obviously inhibited the over-production and release of inflammatory mediator NO induced by LPS / IFN-γ.