Synthesis and Antitumor Activity Evaluation of 3,6-Substituted- 1,2,4-triazolo[3,4-a]phthalazine Derivatives

doi:10.6023/cjoc201602004

Chin. J. Org. Chem. ›› 2016, Vol. 36 ›› Issue (7): 1626-1635.DOI: 10.6023/cjoc201602004 Previous Articles Next Articles

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3,6-取代-1,2,4-三氮唑[3,4-a]酞嗪衍生物的合成和抗肿瘤活性评价

王超杰^a,b, 曹钦坡^a,b, 杨慧^a,b, 宋攀攀^a,b, 薛登启^a,b, 崔飞^a,b, 顾一飞^a,b, 张孝松^a,b, 田亚楠^a, 张秋荣^a,b, 刘宏民^a,b

a. 郑州大学药学院郑州 450001;
b. 新药创制与药物安全性评价河南省协同创新中心郑州 450001

收稿日期:2016-02-01 修回日期:2016-03-03 发布日期:2016-03-28
通讯作者: 张秋荣, 刘宏民 E-mail:zqr406@sina.com;liuhm@zzu.edu.cn
基金资助:
国家自然科学基金（No.81430085）、河南省科技厅基础（No.142300410328）资助项目.

Synthesis and Antitumor Activity Evaluation of 3,6-Substituted- 1,2,4-triazolo[3,4-a]phthalazine Derivatives

Wang Chaojie^a,b, Cao Qinpo^a,b, Yang Hui^a,b, Song Panpan^a,b, Xue Dengqi^a,b, Cui Fei^a,b, Gu Yifei^a,b, Zhang Xiaosong^a,b, Tian Yanan^a, Zhang Qiurong^a,b, Liu Hongmin^a,b

a. School of Pharmaceutical Sciences, Zhengzhou 450001;
b. Collaborative Innovation Center of New Drug Research and Saftry Evaluation, Zhengzhou 450001

Received:2016-02-01 Revised:2016-03-03 Published:2016-03-28
Supported by:
Project supported by the National Natural Science Foundation of China (No. 81430085), and the Basic Research Project of Henan Province (No. 142300410328).

1. Synthesis and Antitumor Activity Evaluation of 3,6-Substituted- 1,2,4-triazolo[3,4-a]phthalazine Derivatives.PDF(2136KB)

Abstract

With the aim of obtaining potential antitumor candidates with more efficiency and more economic value. A series of 3,6-substituted-1,2,4-triazolo[3,4-a]phthalazine derivatives were synthesized. The target products were obtained via cyclization, chlorination, substitution, cyclization, substituted with phthalic anhydride used as the starting material. The structures of target products are confirmed by ¹H NMR, ^I3C NMR, HRMS. A series of 3,6-substituted-1,2,4-triazolo[3,4-a] phthalazine derivatives was evaluated for anticancer activity on four human cancer cell lines including EC-9706, HeLa and MCF-7 by MTT assay. Among them, compound 5d was more cytotoxic against EC-9706 and HeLa cell lines, with IC₅₀ values ranging from 3.9 to 4.5 μmol·L^-¹, which are superior or comparable to 5-Fuorouracil. Flow cytometry analysis indicated that compound 5d induced the cellular early apoptosis and cell cycle arrest in G2/M phase in EC-9706.

Key words: Triazole, Phthalazine, Antitumor, Apoptosis, Cell cycle arrest

Cite this article

Wang Chaojie, Cao Qinpo, Yang Hui, Song Panpan, Xue Dengqi, Cui Fei, Gu Yifei, Zhang Xiaosong, Tian Yanan, Zhang Qiurong, Liu Hongmin. Synthesis and Antitumor Activity Evaluation of 3,6-Substituted- 1,2,4-triazolo[3,4-a]phthalazine Derivatives[J]. Chin. J. Org. Chem., 2016, 36(7): 1626-1635.

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3,6-取代-1,2,4-三氮唑[3,4-a]酞嗪衍生物的合成和抗肿瘤活性评价

Synthesis and Antitumor Activity Evaluation of 3,6-Substituted- 1,2,4-triazolo[3,4-a]phthalazine Derivatives

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