2. Academic Validation
  3. Facile and efficient synthesis and biological evaluation of 4-anilinoquinazoline derivatives as EGFR inhibitors

Facile and efficient synthesis and biological evaluation of 4-anilinoquinazoline derivatives as EGFR inhibitors

  • Bioorg Med Chem Lett. 2016 Jun 1;26(11):2589-93. doi: 10.1016/j.bmcl.2016.04.032.
Zheng Wang 1,  Xue Wu 2,  Li Wang 1,  Jiao Zhang 1,  Jianli Liu 3,  Zhongxing Song 1,  Zhishu Tang 4
Affiliations

Affiliations

  • 1 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.
  • 2 Department of Burns and Cutaneous Surgery, Xijing Hospital, Xi'an 710032, China.
  • 3 Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an 710069, China.
  • 4 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. Electronic address: zst6565@126.com.
PMID: 27118497 DOI: 10.1016/j.bmcl.2016.04.032
Abstract

Series of 4-anilinoquinazoline derivatives were conveniently and efficiently synthesized and their antitumor activities were evaluated by MTT assay in three human Cancer cell lines: H1975, HepG2 and SMMC-7721. New compounds 19a-19h were designed and synthesized to seek for powerful EGFR inhibitors and to explore whether methyl group at C-2 position of quinazoline ring has a positive effect on EGFR inhibition. All the compounds of 19a-19h were found potent against all three cell lines and five compounds (19c, 19d, and 19f-19h) were found more potent against H1975 than gefitinib. SAR studies revealed that methyl group at C-2 position of quinazoline ring could significantly improve the antitumor potency of 4-anilinoquinazolines. The same conclusion was also drawn according to the results of Western blotting analysis. Among all the tested compounds, 19g exhibited extremely potent against H1975 with an IC50 value of 0.11μM, remarkably lower than that of gefitinib (1.23μM). The results of western blotting analysis showed that compounds 19c and 19g could notably inhibit the expression of phosphorylated EGFR, especially 19g, almost inhibited completely.

Keywords

4-Anilinoquinazoline; MTT assay; Synthesis; Western blotting analysis.

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