Synthesis and antitumor activity of novel 6,7,8-trimethoxy N-aryl-substituted-4-aminoquinazoline derivatives

Abstract A series of 6,7,8-trimethoxy N-aryl-substituted-4-aminoquinazoline derivatives were synthesized as epidermal growth factor receptor (EGFR) inhibitors, and their antitumor activities were assessed in the gastric cancer cell line SGC7901 using MTT assay. All compounds of Tg1 – 14 were found to inhibit SGC7901 cell proliferation, and compound Tg11 (IC 50  = 0.434 μM) was found to be slightly more effective against SGC7901 cells than epirubicin (IC 50  = 5.16 μM). This suggests that compound Tg11 can be used as a new substitution structure to develop more efficacious antitumor agents. Western blot analysis showed that treatment with Tg11 (40 μM for 30 min) resulted in near complete inhibition of EGF-induced ERK1/2 phosphorylation, indicating that its anti-proliferative effect is largely associated with inhibition of ERK1/2 activation. These data imply that Tg11 is a potential anticancer agent capable of inhibiting cell proliferation.