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

作　　者：琚立萍 席建军[1] 赵艳梅[1] 何若愚 张建康[1] 史婷婷[1] 刘寿荣[1] 庄让笑[1] JU Liping, XI Jianjun, ZHAO Yanmei, HE Ruoyu, ZHANG Jiankang, SHI Tingting, LIU Shourong, ZHUANG Rangxiao(Hangzhou Xixi Hospital Affiliated Zhejiang Chinese Medical University, Hangzhou 310023, Chin)

机构地区：[1]浙江中医药大学附属杭州市西溪医院,杭州310023

出　　处：《中国现代应用药学》2018年第3期340-344,共5页Chinese Journal of Modern Applied Pharmacy

基　　金：杭州市科技发展计划项目(20142013A60;20152013A03)

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H_2O_2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H_2O_2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H_2O_2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H_2O_2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。OBJECTIVE To design and synthesis a series of N-acetylcysteine derivatives, as well as evaluate the protective effects of the target compounds on H_2O_2-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 H_2O_2 into the LO2 cells. The effects of different concentrations of H_2O_2 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 1 H-NMR, 13 C-NMR and ESI-MS. The target compounds could alleviate H_2O_2-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 H_2O_2.

关 键 词：N-乙酰半胱氨酸 肝损伤 二硫键 硫酯键 活性评价 

分 类 号：R914.2[医药卫生—药物化学]