Design, Synthesis and Antitumor Activities of Novel Quinazolinone Derivatives as Potential EGFR Inhibitors

Abstract

Human epidermal growth factor (EGFR) is an important target for antitumor drug research. A series of novel quinazolinone derivatives were synthesized and developed as potent inhibitors of EGFR. The results showed that most of the aimed compounds had potential anti-tumor cell proliferation activities. Some compounds were tested for their EGFR inhibitory activity. Especially, compound 6d showed the most potent antitumor activity with IC₅₀ values of 1.58 µM against human breast cancer (MCF-7) cell lines and exhibited the most potent EGFR inhibitory activity with IC₅₀ of 0.77 µM. Docking simulation was performed to position compound 6d into the EGFR active site to determine the probable binding conformation.