Synthesis and anticancer activities of 5,6,7-trimethoxy-N-phenyl(ethyl)-4-aminoquinazoline derivatives

Abstract

A series of 5,6,7-trimethoxy-N-phenyl(ethyl)-4-aminoquinazoline compounds was prepared by microwave irradiation and conventional heating methods. Compounds 6p, 6q, and 6x strongly inhibited extracellular regulated kinase1/2 (ERK1/2) phosphorylation induced by epidermal growth factor (EGF) at 1.28 μM in PC3 cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that all compounds had certain anticancer activities, and the IC₅₀ values of 6x were 6.2 ± 0.9, 3.2 ± 0.1, and 3.1 ± 0.1 μM against PC3, BGC823, and Bcap37 cells, respectively. Acridine orange/ethidium bromide staining, Hoechst 33258 staining, DNA ladder, and flow cytometry analyses revealed that 6x induced cell apoptosis in PC3 cells, with apoptosis ratios of 11.6% at 1 μM and 31.8% at 10 μM after 72 h.

Keywords: (1)H NMR; (13)C NMR; (13)C nuclear magnetic resonance; 10-hydroxyl camptothecine; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; AO/EB; Anticancer; Antiphosphorylation; CH; Cell apoptosis; DMF; DMSO; EGF; EGFR; ERK1/2; ESI-MS; HCPT; IR; MTT; MW; N,N-dimethylformamide; Quinazoline; acridine orange/ethidium bromide; conventional heating; dimethyl sulfoxide; electrospray ionization mass spectrometry; epidermal growth factor; epidermal growth factor receptor; extracellular regulated kinase1/2; infra-red; microwave irradiation; proton nuclear magnetic resonance.