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Chinese Journal of Organic Chemistry >

2020 , Vol. 40 >Issue 7: 1967 - 1974

DOI: https://doi.org/10.6023/cjoc202002036

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

  • 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
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  • 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

Received date: 2020-02-26

  Revised date: 2020-04-13

  Online published: 2019-05-06

Supported by

Project supported by the National 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).

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Abstract

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.

Key words： benzothiazole; 4-aminoquinazoline; synthesis; antiproliferative activity

Cite this article

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/cjoc202002036

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