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4-苯胺喹唑啉类化合物是一类具有EGFR激酶抑制活性的喹唑啉类生物碱。本文共合成了13个6位亚胺取代的4-苯胺喹唑啉类化合物,并通过MTT和Western blotting实验对其体外抗肿瘤活性进行了评价。其中化合物13a~13l是新化合物。MTT实验以人肺癌细胞株A549、肝癌细胞株Hep G2和SMMC7721为试药细胞株,结果表明化合物13i和13j对3种试药细胞株都表现出良好的抑制活性。化合物14是不含亚胺取代的4-苯胺喹唑啉,对人肺癌细胞株A549具有显著的抑制活性。通过Western blotting实验研究化合物14和13j对人肺癌细胞A549内EGFR磷酸化水平的影响,结果表明这两个化合物都能显著地抑制EGFR的磷酸化。其中化合物14的抑制强度与阳性对照gefitinib相当,而化合物13j的抑制作用强于gefitinib。
4-Anilinoquinazolines are a class of quinazoline alkaloids with EGFR kinase inhibitory activity. Thirteen 6-imine-substituted 4-anilinoquinazoline compounds were synthesized in this paper. The anti-tumor activity in vitro was evaluated by MTT and Western blotting. Among them, compounds 13a ~ 131 are new compounds. MTT assay of human lung cancer cell line A549, liver cancer cell lines Hep G2 and SMMC7721 as a test cell strain, the results showed that compounds 13i and 13j on the three kinds of drug-resistant cell lines showed good inhibitory activity. Compound 14 is an imine-substituted 4-anilinoquinazoline and has significant inhibitory activity against human lung cancer cell line A549. The effects of 14 and 13j on the phosphorylation level of EGFR in human lung cancer A549 cells were studied by Western blotting. The results showed that both compounds could significantly inhibit the phosphorylation of EGFR. Among them, the inhibitory strength of compound 14 was comparable to the positive control gefitinib, while the inhibitory effect of compound 13j was stronger than that of gefitinib.