Citation: Zhang Luye, Zhang Yang, Wang Zhengjie, Wang Tao, Liu Limin, Liu Xiujuan, Li Erdong, Song Panpan, Zheng Jiaxin, Ke Yu, Shan Lihong, Liu Hongmin, Zhang Qiurong. Synthesis and Antitumor Activity of Novel 4-Aminoquinazoline Derivatives Containing Benzothiazole[J]. Chinese Journal of Organic Chemistry, ;2020, 40(7): 1967-1974. doi: 10.6023/cjoc201902036 shu

Synthesis and Antitumor Activity of Novel 4-Aminoquinazoline Derivatives Containing Benzothiazole

Zhang Luye ^a,b ,
Zhang Yang ^a,b ,
Wang Zhengjie ^a,b ,
Wang Tao ^a,b ,
Liu Limin ^a,b ,
Liu Xiujuan ^a,b ,
Li Erdong ^a,b ,
Song Panpan ^a,b ,
Zheng Jiaxin ^a,b ,
Ke Yu ^a,b ,
Shan Lihong ^a,d ,
Liu Hongmin ^a,b,c,d,, ,
Zhang Qiurong ^a,b,d,,

a.
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001
b.
Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou 450001
c.
State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou 450052
d.
Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou 450001

Corresponding author: Liu Hongmin, liuhm@zzu.edu.cn Zhang Qiurong, zqr409@yeah.net; shlh@zzu.edu.cn
Received Date: 26 February 2020
Revised Date: 13 April 2020

Fund Project: and the Key Research Program of Proteins 2018YFE0195100and the Openning Fund from State Key Laboratory of Esophageal Cancer Prevention & Treatment K2020000XNational Natural Science Foundation of China (No. U1904163) and the Key Research Program of Proteins (No. 2018YFE0195100) and the Openning Fund from State Key Laboratory of Esophageal Cancer Prevention & Treatment (No. K2020000X)National Natural Science Foundation of China U1904163

Figures(3)

In order to find efficient and low toxicity anti-tumor drugs, a series of novel 4-aminoquinazoline derivatives containing benzothiazole were designed and synthesized. And their antiproliferative activities against four human cancer cell lines[human breast cancer cell line (MCF-7), human gastric carcinoma cell line (MGC-803), human prostate cancer cell line (PC-3), human gastric carcinoma cell line (HGC-27)] were evaluated by using methyl thiazolyl tetrazolium (MTT) assay. The results showed that most compounds exhibited good antiproliferative activities against the four human tumor cell lines. Among them, 2-((benzo[d]thiazol-2-ylmethyl)thio)-N-(3-chloro-4-fluorophenyl)-quinazolin-4-amine (13n) showed the best antiproliferative activity against MCF-7, MGC 803, PC-3 and HGC-27 cancer cell lines, with IC₅₀ values of (6.01±0.54), (7.63±0.48), (6.16±0.34), (7.59±0.62) μmol·L^-1, respectively. Its activity was better than the positive control gefitinib. Molecular docking showed that compound 13n could bind well with epidermal growth factor receptor (EGFR). In a nutshell, this work provides clues to discover antitumor agent based on the quinazoline scaffold.
- benzothiazole,
- 4-aminoquinazoline,
- synthesis,
- antiproliferative activity
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