靛红杂合喹唑啉类化合物的合成及抗肿瘤活性研究
收稿日期: 2017-01-18
修回日期: 2017-02-20
网络出版日期: 2017-03-08
基金资助
国家自然科学基金（No.21272144）资助项目.
Synthesis and Antitumor Activity of Heterozygous Isatin-Quinazoline Compounds
Received date: 2017-01-18
Revised date: 2017-02-20
Online published: 2017-03-08
Supported by
Project supported by the National Natural Science Foundation of China (No.21272144) s
合成了9种靛红杂合的喹唑啉类目标化合物，借助NMR、IR和HRMS对目标化合物进行了结构表征，并通过晶体的培养及X射线衍射数据进一步确定了目标化合物的结构.同时采用噻唑蓝（MTT）法在人结直肠癌细胞SW480、人非小细胞肺癌细胞A549和NCI- H1975、人表皮鳞癌细胞A431上对这些化合物进行了抗肿瘤活性的初步体外评价.结果表明，大部分目标化合物具有明显的抑制肿瘤细胞增殖的作用，尤其是化合物（E）-3-（（（E）-（5-（4-（3-乙炔苯胺基）喹唑啉-6-基）呋喃-2-基）亚甲基）亚肼基）吲哚啉-2-酮（4a），在4种所试肿瘤细胞上均表现出良好的抑制肿瘤细胞增殖的作用，其效果优于临床使用的抗肿瘤药物拉帕替尼.
张颖, 吕梦娇, 张娅玲, 陈丽, 王伟, 李宝林 . 靛红杂合喹唑啉类化合物的合成及抗肿瘤活性研究[J]. 有机化学, 2017 , 37(7) : 1787 -1793 . DOI: 10.6023/cjoc201701037
Nine new heterozygous isatin-quinazoline compounds were synthesized from cheap and easily available ortho nitrobenzaldehyde as the starting material. The chemical structures of the synthesized compounds were characterized by NMR, IR and HRMS. The structure of (E)-3-(((E)-(5-(4-((3-ethynylphenyl)amino)quinazolin-6-yl)furan-2-yl)methylene)hydrazono)-indolin-2-one (4a) was further determined by crystallization and X-ray diffraction, and the data revealed that its cis-trans isomerism was (E, E). The antitumor activity of these new compounds was evaluated in vitro by methyl thiazolyl tetrazolium (MTT) assay in human colorectal carcinoma cells SW480, human non-small cell lung cancer cells A549 and NCI- H1975, and human epidermoid squamous carcinoma cells A431. The preliminary data demonstrated that most of the synthetic compounds had moderate to potent inhibitory activity against these four tumor cell lines. In particular, compound 4a had highly potent inhibitory activity on proliferation of four cell lines, and the activity was more potent than positive lapatinib.
Key words： isatin; quinazoline; synthesis; antitumor activity
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