新型蛇葡萄素衍生物γ-聚谷氨酸蛇葡萄素酯的合成、表征及抗肿瘤作用评价  

Synthesis,Characterization and Anti-tumor Effect Evaluation of Novel Ampelopsin Derivative Poly(γ-glutamic Acid)-ampelopsin Conjugate

作　　者：吴晓珊[1] 倪峰[1] 高毓瀅 黄仁杰[1] WU Xiaoshan;NI Feng;Gao Yuying;HUANG Renjie(Dept.of Pharmacy,Fujian Health College,Fuzhou 350101,China;Dept.of Biotechnology,Chia-Nan University of Pharmacy and Science,Taiwan 71710,China)

机构地区：[1]福建卫生职业技术学院药学系,福州350101 [2]嘉南药理大学生物科技系,中国台湾71710

出　　处：《中国药房》2020年第22期2720-2725,共6页China Pharmacy

基　　金：福建省自然科学基金资助项目(No.2018J01118);福建省中青年教师教育科研项目(No.JA15784)。

摘　　要：目的:设计合成γ-聚谷氨酸蛇葡萄素酯(γ-PGA-AMP),并进行表征和体外抗肿瘤活性评价。方法:利用酯化反应将蛇葡萄素接载在γ-聚谷氨酸上生成合成产物。采用紫外光谱法、傅里叶红外光谱法、氢-1核磁共振法及元素分析等方法对合成产物的结构进行表征;采用紫外吸收光谱法在293 nm波长处测定合成产物中蛇葡萄素的含量。以5-氟尿嘧啶为阳性对照,采用MTT法检测γ-PGA-AMP、蛇葡萄素对人乳腺癌细胞MCF-7、人肝癌细胞HepG2、人肺癌细胞A549的抑制作用,计算半数抑制浓度(IC50)。结果:表征结果显示,蛇葡萄素的7位游离羟基与γ-聚谷氨酸a位碳上的羧基已发生了酯化反应,合成产物即为γ-PGA-AMP(产率为55.7%),其中蛇葡萄素含量为32.3%。γ-PGA-AMP和蛇葡萄素对MCF-7、HepG2和A549细胞均有明显的抑制作用;γ-PGA-AMP对上述3种肿瘤细胞的IC50分别为40.19、28.29、55.23μg/mL,蛇葡萄素的IC50分别为105.30、81.23、130.10μg/mL,5-FU的IC50分别为24.72、87.98、30.99μg/m L。结论:成功合成具有体外抗肿瘤活性的γ-PGA-AMP,且抗肿瘤活性强于蛇葡萄素。OBJECTIVE:To design and synthesize poly(γ-glutamic acid)-ampelopsin(γ-PGA-AMP),and to characterize it and evaluate its anti-tumor activity in vitro.METHODS:Synthetic product was produced through an esterification reaction betweenγ-PGA and ampelopsin.The structure of synthetic product was characterized by the UV spectrophotometry,Fourier transform infrared(FT-IR)spectroscopy,1 H-NMR spectra and the quantitative elemental analysis.The content of ampelopsin in synthetic product was determined by UV absorption spectrometry at 292 nm.Using 5-FU as positive control,MTT assay was used to determine inhibitory effects ofγ-PGA-AMP and ampelopsin on human breast cancer cell MCF-7,human liver cancer cell HepG2 and human lung cancer cell A549.The IC50 was calculated.RESULTS:The results showed that the free 7-hydroxyl group of ampelopsin and the a-carboxyl group ofγ-polyglutamic acid had been esterified to obtainγ-PGA-AMP;the yield ofγ-PGA-AMP was 55.7%,and the content of ampelopsin was 32.3%.The inhibitory effect ofγ-PGA-AMP and ampelopsin on MCF-7,HepG2 and A549 cells was obvious.IC50 ofγ-PGA-AMP(to 3 above tumor cells)were 40.19,28.29 and 55.23μg/m L,those of ampelopsin were 105.30,81.23,130.10μg/m L,those of 5-FU were 24.72,87.98,30.99μg/mL,respectively.CONCLUSIONS:γ-PGA-AMP with anti-tumor effect in vitro is synthesized successfully,and its anti-tumor effect is stronger than that of ampelopsin.

关 键 词：蛇葡萄素 Γ-聚谷氨酸 高分子化合物 合成 表征 抗肿瘤作用 

分 类 号：R284.3[医药卫生—中药学] R979.1[医药卫生—中医学]