新型含二硫键和硫酯键的乙酰半胱氨酸衍生物的合成与抗肝损伤活性评价

Synthesis and Anti-liver Injury Activities Evaluation of Novel Acetylcysteine Derivatives with Disulphide and Thioester Bonds

关键词:  N-乙酰半胱氨酸  肝损伤  二硫键  硫酯键  活性评价

Key words:  N-acetylcysteine  liver injury  disulphide bonds  thioester bonds  biological evaluation

摘要:

目的 设计、合成N-乙酰半胱氨酸衍生物，并评价目标化合物对H₂O₂诱导的LO2细胞氧化损伤的保护作用。方法 以L-半胱氨酸和N-乙酰半胱氨酸为起始原料，采用酰氯酯化法合成具有全新结构的乙酰半胱氨酸衍生物；以H₂O₂损伤LO2人肝细胞建立体外氧化损伤模型，利用CCK-8法检测不同浓度H₂O₂对LO2细胞存活率的影响，并检测细胞上清中MDA含量和SOD活性。结果 共合成了6个全新结构的N-乙酰半胱氨酸衍生物，其结构经¹H-NMR、¹³C-NMR、ESI-MS确证，目标化合物能够抑制H₂O₂诱导的LO2氧化损伤，并能够降低MDA含量和提高SOD活性（P<0.01或P<0.05）。结论 本研究快速、高效地合成了N-乙酰半胱氨酸系列衍生物，目标化合物对体外肝细胞损伤具有保护作用。

Abstract:

OBJECTIVE To design and synthesis a series of N-acetylcysteine derivatives, as well as evaluate the protective effects of the target compounds on H₂O₂-induced oxidative injury on LO2 cells. METHODS A series of novel N-acetylcysteine derivatives were synthesized by acyl chloride esterification method from L-cysteine and N-acetylcysteine. The in vitro oxidative injury model was established by inducing H₂O₂ into the LO2 cells. The effects of different concentrations of H₂O₂ on the LO2 cell survival rates were detected by CCK-8 kit, and the contents of MDA and the activities of SOD were measured in the cell culture supernate. RESULTS Six novel N-acetylcysteine derivatives were synthesized and the structures were confirmed by ¹H-NMR, ¹³C-NMR and ESI-MS. The target compounds could alleviate H₂O₂-induced oxidative injury on LO2 cells, reduce the concentrations of MDA and increase the activities of SOD(P<0.01 or P<0.05). CONCLUSION A series of novel N-acetylcysteine derivatives are designed and synthesized, which display protective effects on hepatocytes injury induced by H₂O₂.