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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05期

页码:

381-385

栏目:

基础医学

出版日期:

2016-09-20

文章信息/Info

Title:

Synthesis and evaluation of furanoid podophyllotoxin derivatives with? ?anticancer activity

文章编号:

1006-8147（2016）05-0381-05

作者:

成伟华¹; 2; 牛聪³; 孙强稳⁴; 陈虹⁵; 邹忠梅²

(;1.中国医学科学院北京协和医学院药用植物研究所,北京100193; 2.原子高科股份有限公司,北京 102413; 3. 武警总医院医务部,北京100039;4.武警8720部队医院药械科,无锡 214000;5.武警后勤学院生药学教研室,天津300309)

Author(s):

CHENG Wei-hua ¹;  2;  NIU Cong ³; SUN Qiang-wen ⁴; CHEN Hong ⁵; ZOU Zhong-mei ²

(1. Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China; 2. AtomHigh. TechCo. LTD, Beijing 102413, China; 3. General Hospital of Chinese People’s Armed Police Forces, Beijing 100039, China; 4. 8720 Hospital of Chinese People’s Armed Police Forces, Wuxi 214000, China; 5. Pharmacognosy Division, Medical College of Chinese Peoples Armed Police Force, Tianjin 300162, China)

关键词:

鬼臼毒素; 结构修饰; 抗肿瘤活性

Keywords:

podophyllotoxin;  structure modification;  antitumor activity

分类号:

R9

DOI:

-

文献标志码:

A

摘要:

目的：获得抗肿瘤活性更强的鬼臼毒素衍生物。方法：以鬼臼毒素为起始原料，通过把取代呋喃和鬼臼毒素拼接，设计并合成5个4β-N-取代呋喃鬼臼毒素衍生物，目标产物的结构通过¹H-NMR, ¹³C-NMR和HRMS的确证，同时采用 MTT 法评价了新化合物对HeLa, K562和K562/A02的细胞毒活性。结果: 合成的5个化合物中具有确切的细胞毒活性，其中化合物7c和11b对于耐药肿瘤细胞K562/A02的活性明细优于阳性对照依托伯苷。结论：把取代呋喃连接到鬼臼毒素可以增加抗肿瘤活性。

Abstract:

Objective: To acquire novel podophyllotoxin derivatives with higher antitumor activity. Methods：The podophyllotoxin derivatives were synthesized using podophyllotoxin as the starting material through substituted furfuran and success split joint podophyllotoxin. five 4β-N-substituted furfuran podophyllotoxin derivatives were designed, synthesized, and confirmed by ¹H-NMR, ¹³C-NMR and HRMS, In vitro, cytotoxieities were tested against three human tumor cells (HeLa, K562, K562/A02) by MTT. Results: All compounds showed improved activities against HeLa and K562 when compared with VP-16. In particular, compound 7c, 11b exhibited the most potent activity toward drug-resistant K562/A02 cells, as compared to VP-16. Conclusion: Substituted furan connected to the podophyllotoxin could increase antitumor activity.

参考文献/References:

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相似文献/References:

[1]李楠,等.鬼臼毒素脲类衍生物的合成和体外抗癌活性的研究[J].天津医科大学学报,2016,22(03):199.
　LI Nan,ZHAO Yang,WEI Fei,et al.Synthesis and biological evaluation of 4-ureido podophyllotoxin derivatives as anticancer agents [J].Journal of Tianjin Medical University,2016,22(05):199.

备注/Memo

备注/Memo:

基金项目 国家自然科学基金资助项目（30873363）；国家"重大新药创制"科技重大专项(2011ZX09307-002-01 、2013ZX09508104)

作者简介 成伟华（1985-），男，助理研究员，博士，研究方向：天然产物结构修饰及放射性药物研究；通信作者：邹忠梅，E-mail：zmzou@implad.ac.cn。

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更新日期/Last Update: 2016-09-19