摘要/Abstract

为了寻找高效低毒的抗肿瘤药物，设计并合成了一系列新型的含苯并噻唑结构的4-氨基喹唑啉类衍生物，并采用噻唑蓝（MTT）法测定了目标化合物对人乳腺癌细胞系（MCF-7）、人胃癌细胞系（MGC-803）、人前列腺癌细胞系（PC-3）和人高度分化的胃癌细胞系（HGC-27）四种肿瘤细胞的抗增殖活性.结果显示大部分化合物具有较好的抗肿瘤活性，其中2-（（苯并[d]噻唑-2-基甲基）硫亚基）-N-（3-氯-4-氟苯基）-喹唑啉-4-胺（13n）对MCF-7、MGC-803、PC-3和HGC-27四种细胞显示出最好的抗增殖活性，IC₅₀值分别为（6.01±0.54），（7.63±0.48），（6.16±0.34）和（7.59±0.62） μmol·L^-1，其活性均优于阳性对照物吉非替尼.分子对接结果显示化合物13n能与表皮生长因子受体（EGFR）很好地结合，为抗肿瘤药物的研究提供了线索.
关键词: 苯并噻唑, 4-氨基喹唑啉, 合成, 抗肿瘤活性
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


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