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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:

22卷

期数:

2016年03期

页码:

199

栏目:

基础医学

出版日期:

2016-05-20

文章信息/Info

Title:

Synthesis and biological evaluation of 4-ureido podophyllotoxin derivatives as anticancer agents

文章编号:

1006-8147（2016）03-0199-05

作者:

?李楠¹; 3; ;  赵阳¹; 3; 

?

(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.天津中医药大学研究生院,天津300193;3.中国人民武装警察部队后勤学院生药与药剂学教研室,天津300309)

Author(s):

LI Nan¹; 3; ZHAO Yang¹; 3; WEI Fei²; GAO Chen-guang³; CAO Bo³; GAO Ying³; CHEN Hong¹; 3

(1.School of Pharmacy, Tianjin Medical University, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, Tianjin300070,China;2.Graduate School，Tianjin University of Traditional Chinese Medicine,Tianjin 300193;3.Department of Pharmacognosy, Logistic University of PAP, Tianjin 300309, China)

关键词:

鬼臼毒素; 脲; N; N’-羰基二咪唑; 抗肿瘤活性

Keywords:

podophyllotoxins;  urea;  N;  N’- carbonyldiimidazole;  antitumor activity

分类号:

R9

DOI:

-

文献标志码:

A

摘要:

?目的：为了得到抗癌活性更高的抗肿瘤药物，设计、合成新型脲类鬼臼毒素衍生物。方法：以鬼臼毒素或4’-去甲基鬼臼毒素为起始原料经N, N’-羰基二咪唑 (CDI)活化其C-4位氨基，并与仲胺类化合物进行缩合反应，得到鬼臼毒素脲类衍生物，经氢谱和高分辨质谱对其进行结构表征。采用噻唑蓝（MTT）法测试目标化合物对人白血病（K562）和人宫颈癌（Hela）细胞的体外抗肿瘤活性。结果：合成8个新的目标化合物，其中化合物6a增殖抑制活性较强。结论：在鬼臼毒素C-4位引入哌嗪环脲类结构可提高其体外抗肿瘤活性。

Abstract:

Objective: To obtain anticancer agents with higher efficiency through a novel series of 4-ureido podophyllotoxin derivatives. Methods: The novel target compounds were synthesized by reacting podophyllotoxin or 4’-demethylepipodophyllotoxin with secondary amines under catalytic agent N, N’-carbonyldiimidazole(CDI). All the compounds were characterized by ¹H-NMR and HR-MS. Meanwhile, MTT assay was used to test their cytotoxicity against K562 and Hela cell lines. Results: Eight novel target compounds were synthesized. Among them, compound 6a exhibits was identified to have stronger inhibition effect. Conclusion: The anticancer activity of podophyllotoxin could be improved when itAs C-4 is combined with the structure of ureido and piperazidine.

参考文献/References:

[1] 杨显志, 邵华, 张玲琪. 鬼臼毒素资源研究现状[J]. 中草药, 2001, (11): 85
[2] Liu X, Zhang L L, Xu X H, et al. Synthesis and anticancer activity of dichloroplatinum (II) complexes of podophyllotoxin[J]. Bioorg Med Chem Lett, 2013, 23(13): 3780
[3] Choi J Y, Cho H J, Hwang S G, et al. Podophyllotoxin acetate enhances γ-ionizing radiation-induced apoptotic cell death by stimulating the ROS/p38/caspase pathway[J]. Biomed Pharmacother, 2015, (70): 111
[4] Kamal A, Telukutla S, Polepalli S, et al. Synthesis and biological evaluation of 4-aza-2, 3-dihydropyridophenanthrolines as tubulin polymerization inhibitors[J]. Bioorg Med Chem Lett, 2014, 24(15): 3356
[5] Liu J F, Sang C Y, Xu X H, et al. Synthesis and cytotoxic activity on human cancer cells of carbamate derivatives of 4β-(1, 2, 3-triazol-1-yl) podophyllotoxin[J]. Eur J Med Chem, 2013, (64): 621
[6] Kamal A, Suresh P, Ramaiah M J, et al. 4β-[4′-(1-(Aryl) ureido) benzamide] podophyllotoxins as DNA topoisomerase I and IIα inhibitors and apoptosis inducing agents[J]. Bioorg Med Chem, 2013, 21(17): 5198
[7] Zhang Z J, Tian J, Wang L T, et al. Design, synthesis and cytotoxic activity of novel sulfonylurea derivatives of podophyllotoxin[J]. Bioorg Med Chem, 2014, 22(1): 204
[8] Ai T, Shi S Y, Chen L T, et al. Synthesis and anti-tumor activity evaluation of novel podophyllotoxin derivatives[J]. Chinese Chemical Letters, 2013, 24(1): 37.
[9] 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
[10] 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

相似文献/References:

[1]成伟华,牛聪,孙强稳,等.呋喃鬼臼毒素衍生物及其抗肿瘤活性研究[J].天津医科大学学报,2016,22(05):381.
　CHENG Wei-hua,NIU Cong,et al.Synthesis and evaluation of furanoid podophyllotoxin derivatives with? ?anticancer activity[J].Journal of Tianjin Medical University,2016,22(03):381.

备注/Memo

备注/Memo:

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

作者简介 李楠（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。

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更新日期/Last Update: 2016-05-24