Synthesis and Antitumor Activity of Sorafenib Analogs Containing a Tetrazole Moiety

doi:10.1007/s40242-018-8236-5

高等学校化学研究 ›› 2019, Vol. 35 ›› Issue (1): 41-46.doi: 10.1007/s40242-018-8236-5

Synthesis and Antitumor Activity of Sorafenib Analogs Containing a Tetrazole Moiety

TIAN Ye¹, YU Simiao¹, CAI Lude¹, GONG Guowei², WU Guodong¹, QI Hongxia³, ZHAO Yanfang¹, QIN Mingze¹

1. Key Laboratory of Structure-based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, P. R. China;
2. Department of Bioengineering, Zhuhai Campus of Zunyi Medical University, Zhuhai 519041, P. R. China;
3. Shengjing Hospital of China Medical University, Shenyang 110016, P. R. China

收稿日期:2018-07-20 修回日期:2018-10-25 出版日期:2019-02-01 发布日期:2018-11-12
通讯作者: ZHAO Yanfang, QIN Mingze E-mail:yanfangzhao@126.com;qinmingze001@126.com
基金资助:
Supported by the National Natural Science Foundation of China(No.81502924).

Synthesis and Antitumor Activity of Sorafenib Analogs Containing a Tetrazole Moiety

TIAN Ye¹, YU Simiao¹, CAI Lude¹, GONG Guowei², WU Guodong¹, QI Hongxia³, ZHAO Yanfang¹, QIN Mingze¹

1. Key Laboratory of Structure-based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, P. R. China;
2. Department of Bioengineering, Zhuhai Campus of Zunyi Medical University, Zhuhai 519041, P. R. China;
3. Shengjing Hospital of China Medical University, Shenyang 110016, P. R. China

Received:2018-07-20 Revised:2018-10-25 Online:2019-02-01 Published:2018-11-12
Contact: ZHAO Yanfang, QIN Mingze E-mail:yanfangzhao@126.com;qinmingze001@126.com
Supported by:
Supported by the National Natural Science Foundation of China(No.81502924).

摘要/Abstract

摘要： A novel series of diaryl biuret derivatives containing a tetrazole moiety was designed and synthesized. All the target compounds were evaluated for their in vitro antitumor activity against HT-29, HepG2, MCF-7 and A549 cells by MTT assay. Most of them exhibited obvious antitumor activity, and four of them (4a, 4c, 4h and 7a) were superior to sorafenib in general. Among them, Compound 4h displayed more potent activity than sorafenib in all tested cancer cells. Compound 4c exhibited the most outstanding activity in inhibition of growth of HepG2 cells (IC₅₀=0.55 μmol/L). Further, they both revealed favorable metabolic stability in in vitro assay. Compounds 4c and 4h are promising candidates for further development.

关键词: Sorafenib derivative, Tetrazole moiety, Antitumor activity

Abstract: A novel series of diaryl biuret derivatives containing a tetrazole moiety was designed and synthesized. All the target compounds were evaluated for their in vitro antitumor activity against HT-29, HepG2, MCF-7 and A549 cells by MTT assay. Most of them exhibited obvious antitumor activity, and four of them (4a, 4c, 4h and 7a) were superior to sorafenib in general. Among them, Compound 4h displayed more potent activity than sorafenib in all tested cancer cells. Compound 4c exhibited the most outstanding activity in inhibition of growth of HepG2 cells (IC₅₀=0.55 μmol/L). Further, they both revealed favorable metabolic stability in in vitro assay. Compounds 4c and 4h are promising candidates for further development.

Key words: Sorafenib derivative, Tetrazole moiety, Antitumor activity

TIAN Ye, YU Simiao, CAI Lude, GONG Guowei, WU Guodong, QI Hongxia, ZHAO Yanfang, QIN Mingze. Synthesis and Antitumor Activity of Sorafenib Analogs Containing a Tetrazole Moiety[J]. 高等学校化学研究, 2019, 35(1): 41-46.

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Synthesis and Antitumor Activity of Sorafenib Analogs Containing a Tetrazole Moiety

Synthesis and Antitumor Activity of Sorafenib Analogs Containing a Tetrazole Moiety

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