Design, Synthesis and Structure-Activity Relationship ofTryptanthrins as Antitumor Agents

doi:10.6023/cjoc201507012

Chin. J. Org. Chem. ›› 2016, Vol. 36 ›› Issue (1): 121-129.DOI: 10.6023/cjoc201507012 Previous Articles Next Articles

Articles

色胺酮衍生物设计、合成及抗肿瘤活性构效关系研究

侯宝龙^a, 艾芸^a,b, 王翠玲^a, 张宁^a, 杨柳^a, 刘竹兰^a, 刘建利^a

a 西部资源生物与现代生物技术省部共建教育部重点实验室西北大学生命科学学院西安 710069;
b 西安市食品药品监督检验所西安 710054

收稿日期:2015-07-15 修回日期:2015-09-14 发布日期:2015-09-25
通讯作者: 刘建利 E-mail:jlliu@nwu.edu.cn
基金资助:
陕西省自然科学基金(No. 2014JM4095)、陕西省教育厅基金(No. 12JK1010)和陕西省重点科技创新团队计划(No. 2013KCT-24)资助项目.

Design, Synthesis and Structure-Activity Relationship ofTryptanthrins as Antitumor Agents

Hou Baolong^a, Ai Yun^a,b, Wang Cuiling^a, Zhang Ning^a, Yang Liu^a, Liu Zhulan^a, Liu Jianli^a

a Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an 710069;
b Xi'an Institute for Food and Drug Control, Xi'an 710054

Received:2015-07-15 Revised:2015-09-14 Published:2015-09-25
Supported by:
Project supported by the Shaanxi Provincial Natural Science Fundation (No. 2014JM4095), the Foundation of the Education Department of Shaanxi Province (No. 12JK1010), the Key Program for Science and Technology Innovative Research Team of Shaanxi Province (No. 2013KCT-24).

1. Design, Synthesis and Structure-Activity Relationship ofTryptanthrins as Antitumor Agents.PDF(3175KB)

Abstract

The isatin derivatives 4a～4f were prepared and underwent oxidative hydrolysis to give the anthranilic acid 5a～5d. A and/or D-ring substituted tryptanthrins were designed and synthesized from 4a～4f to 5a～5d. Then C-ring Schiff bases of tryptanthrin were synthesized by condensation of 6-carbonyl with hydrazine and hydroxylamine hydrochloride. Finally, the B-ring was replaced with piperazine to give 11H-indeno[1,2-b]quinoxalin-11-one. 20 compounds were synthesized and their structures were confirmed by ¹H NMR, IR and elemental analysis. To best of our knowledge, 13 of them were unknown in the literature. The antitumor activities of synthesized compounds were evaluated against A549 cell line in vitro. The preliminary results indicated that 1b, 1c, 1i, 1j, 1p and 1q showed good antitumor activity with the IC₅₀ of 3.58, 0.99, 1.03, 2.10, 0.51 and 0.43 μmol·L^－1, respectively. Structure-activity relationship showed that halogen substitution located in the D-ring enhanced the anti-tumor activity, while the same substitution located in the A ring reduced the activity. The anti-tumor activity disappeared when B-ring was replaced by piperazine, while there was no significant difference for tryptanthrin and its C-ring Schiff base.

Key words: tryptanthrin, isatin, anthranilic acid, antitumor activity

Cite this article

Hou Baolong, Ai Yun, Wang Cuiling, Zhang Ning, Yang Liu, Liu Zhulan, Liu Jianli. Design, Synthesis and Structure-Activity Relationship ofTryptanthrins as Antitumor Agents[J]. Chin. J. Org. Chem., 2016, 36(1): 121-129.

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色胺酮衍生物设计、合成及抗肿瘤活性构效关系研究

Design, Synthesis and Structure-Activity Relationship ofTryptanthrins as Antitumor Agents

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