大黄酸衍生物的制备及其抗糖尿病肾病活性研究

目的 设计合成活性优化的新大黄酸衍生物，并对其进行抗糖尿病肾病活性研究。方法 以大黄酸为先导化合物合成了一系列大黄酸酰胺类衍生物；通过实时定量 PCR 实验对其进行糖尿病肾病体外筛选，并通过对糖尿病肾病模型大鼠进行药效学实验研究其降糖活性。结果 合成了11个未见文献报道的新化合物，其结构经元素分析、质谱、核磁共振谱确证。化合物 9 对四型胶原（Col Ⅳ）和胰岛素样生长因子-Ⅰ（IGF-Ⅰ）的基因表达均有下调趋势；高剂量的化合物 9 能显著降低餐后血糖水平（P < 0.001）。结论 大黄酸酰胺类衍生物在治疗糖尿病领域值得进一步研究。

Study on preparation and anti-diabetic nephropathy activities of rhein derivatives

Rhein,a drug treating for diabetic nephropathy,has some adverse effects such as diarrhea and mutagenesis.A series of rhein derivatives,which were the structural optimizations of rhein,were synthesized,and their anti-diabetic nephropathy activities were studied.The general synthetic method was that after chlorination on the 3-COOH of rhein,it was then reacted with primary amine to get final products.Eleven novel compounds were synthesized and their structures were confirmed by 1H-NMR,13C-NMR and MS.The real-...