丹参素川芎嗪偶合物的结构修饰

Modification of Danshensu and tetramethylpyrazine conjugate derivatives

实验室前期研究发现的丹参素川芎嗪偶合物(DTC)具有良好的心肌细胞保护作用,为优化其结构,本研究对其酚羟基与醇羟基部位进行脂肪链的酯键修饰,合成一系列新型衍生物,并测定这些衍生物对叔丁基过氧化氢诱导损伤的H9c2细胞的保护作用,初步探索其构效关系.结果显示,仅在酚羟基上修饰的化合物显示出较好的细胞保护作用;若在酚羟基的修饰基础上,进一步对醇羟基修饰会造成化合物活性下降,且当醇羟基部位修饰基团碳链较长(>3)时,随碳链延长而活性下降明显.该结果对丹参素衍生物构效关系的深入研究奠定了基础.

In this work,a series of Danshensu derivatives were designed,synthesized based on the conjugate of Danshensu and tetramethylpyrazine(DTC).These derivatives were evaluated in protecting H9c2 cells against tert-butyl hydroperoxide induced injury.Biological results revealed that compounds with long chain acyl groups(more than three carbons) at both of alcoholic hydroxyl group and phenolic hydroxyl group showed decreased activities.Derivatives modified only at the phenolic groups could keep DTC's activity.This work provided helpful information of the structure-activity relationship of DSS and could be used for further development of Danshensu derivatives.