4_苯胺喹唑啉衍生物的合成及抗EGFR活性研究_英文_王征.pdfVIP

Acta Pharmaceutica Sinica 2015, 50 (12): 1613−1621 1613 Synthesis of new 4-anilinoquinazoline analogues and evaluation of their EGFR inhibitor activity 1, 2 1 1 1 1 1 WANG Zheng , WANG Cui-ling , Li Jun-lin , ZHANG Ning , SUN Yan-ni , LIU Zhu-lan , TANG Zhi-shu2, LIU Jian-li1* (1. Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi’an 710069, China; 2. Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi Province Key Laboratory of New Drugs and Chinese Medicine Foundation Research, Shaanxi Rheumatism and Tumor Center of TCM Engineering Technology Research, Shaanxi University of Chinese Medicine, Xian Yang 712083, China) Abstract : Thirteen of 4-anilinoquinazoline derivatives with imine groups at position 6 of quinazoline ring were synthesized and their antitumor activities were evaluated by MTT assay and Western blotting analysis. Among these compounds, 13a−13l were reported first time. The MTT assay was carried out on three human cancer cell lines (A549, HepG2 and SMMC7721) with EGFR highly expressed. Among the tested compounds, 13i and 13j exhibited notable inhibition potency and their IC50 values on three cell lines were equivalent to or less than those of gefitinib. Compound 14, without imine group substituted, displayed excellent inhibitor potency only on A549 cell line. Compounds 14 and 13j were chosen to perform Western blotting analysis on A549. The results showed that both of the compoun