Abstract

Previous evidence demonstrated the antitumor ability of quinazolines and its derivatives. In this study, the anticancer activities of N-(4-chlorophenyl)-5,6,7-trimethoxyquinazolin-4-amine dihydrochloride against four kinds of cell lines were evaluated by 3-(4,5-dimeth-ylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The bioassay results indicated that title compound possessed wide spectrum of anticancer activity. Androgen-independent prostate cancer (PC-3) cells were employed and microscopic observation, lactate dehydrogenase (LDH) release assay, and Western blot were performed to study the antitumor mechanism of N-(4-chlorophenyl)-5,6,7-trimethoxyquinazolin-4-amine dihydrochloride against tumor cells. It was found that title compound executed anticancer activity in a dose-dependent manner with 24.46 μM IC₅₀ of 72 h treatment. Microscopic observation and LDH release assay showed that the compound exerted such an effect through antiproliferation pathway rather than cytotoxicity. Furthermore, Western blot analysis revealed that treatment of cells with N-(4-chlorophenyl)-5,6,7-trimethoxyquinazolin-4-amine dihydrochloride (at more than 10 μM for 30 min) resulted in an almost complete inhibition of epidermal growth factor (EGF) induced phosphorylation of extracellular signal-regulated protein kinase1/2 (ERK1/2) which suggests that its antiproliferation effect is linked to its inhibition of ERK1/2 activation. These data imply that N-(4-chlorophenyl)-5,6,7-trimethoxyquinazolin-4-amine dihydrochloride is a potential anticancer agent capable of antiproliferation activity.

Key words: N-(4-chlorophenyl)-5,6,7-trimethoxyquinazolin-4-amine dihydrochloride, prostate cancer (PC-3) cell line, antiproliferation, extracellular signal-regulated protein kinase1/2 (ERK1/2).