| 聚乙二醇缀合熊果酸衍生物的合成及体外抗癌活性 |
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| 引用本文： | 白锴凯,陈芬玲,郭养浩.聚乙二醇缀合熊果酸衍生物的合成及体外抗癌活性[J].中国新药杂志,2012(13):1536-1540. |
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| 作者姓名： | 白锴凯 陈芬玲 郭养浩 |
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| 作者单位： | 福州大学化学化工学院;福建省医疗器械和医药技术重点实验室 |
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| 基金项目： | 福建省自然科学基金(2008J1005);福建省医疗器械与医药技术重点实验室开放基金(200903) |
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| 摘 要： | 目的:合成具有一定水溶性的聚乙二醇(PEG)缀合熊果酸衍生物并考察其体外抗癌活性。方法:以熊果酸(ursolic acid,UA)作为母核,采用PEG、琥珀酸对其C28位进行接合修饰,合成一系列PEG缀合熊果酸衍生物并考察其水溶性和抗癌活性;采用流式细胞术探讨其抗癌机制。结果:所合成系列PEG缀合熊果酸衍生物的水溶性较熊果酸有明显改善,同时具有更显著的体外抗癌活性;化合物8c对5株受试肿瘤细胞的IC50(48 h)均小于10μmol.L-1,将AGS细胞阻滞于G2/M期并具有诱导凋亡作用(凋亡率高于70%)。结论:将熊果酸C28位进行PEG修饰是保持和提高其抗癌活性的有效途径之一。
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| 关 键 词： | 熊果酸 聚乙二醇 衍生物 肿瘤 水溶性 |
Synthesis and in vitro antitumor activity of PEG-conjugated ursolic acid derivatives |
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| BAI Kai-kai,CHEN Fen-ling,GUO Yang-hao.Synthesis and in vitro antitumor activity of PEG-conjugated ursolic acid derivatives[J].Chinese Journal of New Drugs,2012(13):1536-1540. |
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| Authors: | BAI Kai-kai CHEN Fen-ling GUO Yang-hao |
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| Institution: | 1,2(1 College of Chemistry and Chemical Engineering,Fuzhou University,Fuzhou 350108,China; 2 Fujian Key Lab of Medical Instrument and Pharmaceutical Technology,Fuzhou 350002,China) |
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| Abstract: | Objective: To synthesize a series of PEG-conjugated ursolic acid(UA) derivatives with acceptable water-solubility,and to determine their anti-tumor activity.Methods: As a leading compound,UA via its C28 position was conjugated to PEG and succinic acid to prepare PEG-conjugated UA derivatives.Their water-solubility,and cytotoxicity against 5 tumor cell lines were evaluated;the anti-tumor mechanism was investigated by flow cytometry.Results: The water-solubility of these derivatives was obviously improved,and they were more cytotoxic than UA.Among them,the IC50(48 h) of compound 8c was less than 10 μmol·L-1 against all the 5 cell lines.Compound 8c induced cell-cycle arrest in G2/M and apoptosis(>70%) in AGS cells.Conclusion: The conjugate of PEG to C28 of UA is an effective way to develop new UA derivatives with better antitumor activities. |
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| Keywords: | ursolic acid polyethylene glycol derivatives tumor water-solubility |
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