Citation: 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]. Chinese Journal of Organic Chemistry, ;2016, 36(1): 121-129. doi: 10.6023/cjoc201507012 shu

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

Corresponding author: Liu Jianli,
Received Date: 15 July 2015
Revised Date: 14 September 2015

Fund Project: the Key Program for Science and Technology Innovative Research Team of Shaanxi Province 2013KCT-24the Shaanxi Provincial Natural Science Fundation 2014JM4095the Foundation of the Education Department of Shaanxi Province 12JK1010

Figures(5)

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.
- tryptanthrin,
- isatin,
- anthranilic acid,
- antitumor activity
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