|本期目录/Table of Contents|

[1]孙强稳,王 杰,陈守强,等. 新型酰胺类鬼臼毒素衍生物的合成及体外抗肿瘤活性[J].天津医科大学学报,2015,21(04):282-286.
　SUN Qiang-wen,WANG Jie,CHEN Shou-qiang,et al.Synthesis and evaluation of novel podophyllotoxin derivatives as potential antitumor agents[J].Journal of Tianjin Medical University,2015,21(04):282-286.
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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:
21卷
期数:
2015年04期
页码:
282-286
栏目:
基础医学
出版日期:
2015-07-15

文章信息/Info

Title:
Synthesis and evaluation of novel podophyllotoxin derivatives as potential antitumor agents
文章编号:
1006-8147（2015）04-0282-05
作者:
孙强稳1; 2; 王 杰1; 陈守强1; 牛 聪2; 曹 波2; 高 颖2; 陈 虹1; 2

 
 （1.天津医科大学药学院，天津市临床药物关键技术重点实验室，天津 300070;2.武警后勤学院生药学教研室，天津300309）
Author(s):
SUN Qiang-wen1; 2; WANG Jie1; CHEN Shou-qiang1; NIU Cong2; CAO Bo;  GAO Ying;  CHEN Hong2
(1.School of Pharmacy, Tianjin Medical University ，Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics ,Tianjin 300070，China；2.Department of Pharmacognosy， Logistic University of PAPF，Tianjin 300309，China)
关键词:
鬼臼毒素衍生物; 苯甲酸; 肉桂酸; 体外抗肿瘤活性
Keywords:
podophyllotoxin;  benzoic acid;  cinnamic acid;  antitumor activity in vitro
分类号:
R9
DOI:
-
文献标志码:
A
摘要:
目的：通过对鬼臼毒素母核进行结构改造，以获得高效、低毒、抗多药耐药的新型鬼臼毒素衍生物。方法：将4β-氨基-4-脱氧表鬼臼毒素的C-4位经酰胺化分别引入对位取代的苯甲酸和对位取代的肉桂酸化合物，得到4-甲酰基苯甲酸及4-甲酰基肉桂酸的鬼臼毒素类衍生物，通过MTT法筛选，并对K562和Hela细胞进行药理活性评价。结果：合成得到两个系列共8个化合物，所有化合物都经过HR-ESI-MS和1HNMR验证，其中化合物1d、2b具有较强的体外抗肿瘤活性。结论：在C-4位引入4-甲酰基苯甲酸以及4-甲酰基肉桂酸基团可增加鬼臼毒素类衍生物的抗肿瘤活性。
Abstract:
Objective：To obtain novel podophyllotoxin derivatives with higher efficiency, lower toxicity and anti-multi-drug resistance. Methods：Derivatives of 4-formyl benzoicacid and 4-formyl-cinnamic acid in C-4 position of 4β-amino-pipodophyllotoxin were introduced; Hela cells and K562 were used to evaluate pharmacological activity in vitro. Results：Eight compounds by different methods were obtained, and all compounds were confirmed by MS and 1HNMR validation. The compounds 1b,1d,2a and 2b had a good drug resistance in both Hela and K562 cell line. Conclusion：At C-4 position, podophyllotoxin introduced 4-formyl-benzoyl derivatives and 4-formyl-cinnamic acid derivatives show can increase antitumor activities.

参考文献/References:

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[5]Zhang Z H, Zhang L M, Luo G, et al. Synthesis and biological evaluation of novel podophyllotoxin analogs as antitumor agents[J]. J Asian Nat Prod Res, 2014,16(5):527

[6]Cho S J, Tropsha A, Suffness M, et al. Antitumor agents. 163. Three-dimensional quantitative structure-activity relationship study of 4’-O-demethylepipodophyllotoxin analogs using the modified CoMFA/q2-GRS approach[J]. Med Chem, 1996,39(7):1383

[7]Cheng W H, Cao B, Shang H, et al. Synthesis and evaluation of novel podophyllotoxin derivatives as potential antitumor agents[J]. Eur J Med Chem, 2014,85:498

[8]蒋卫华，崔爱军. 肉桂酸合成方法研究进展[J]. 精细石油化工进展, 2013,14(2):34

[9]段华鑫，张殊佳，周鹏. 喜树碱肉桂酸衍生物的合成及其抗肿瘤活性的研究[J]. 有机化学, 2009,29(5):724

[10]卢娟，汪晖，卢方安. 肉桂酸对胃腺癌细胞诱导分化的实验研究[J]. 中国药理学通报, 2007,23(2):237

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备注/Memo

备注/Memo:
基金项目 国家自然科学基金资助项目（30873363）；天津市应用基础基金项目资助（08JCYBJC070000）

作者简介 孙强稳（1990-），男，硕士在读，研究方向：天然产物结构改造；通信作者：陈虹，E-mail: chenhongtian06@163.com。



更新日期/Last Update: 2015-07-16