title: Anti-tumour activity of 4-(4-fluorophenyl)amino-5,6,7-trimethoxyquinazoline against tumour cells in vitro.
abstract: In order to create novel, potent and selective anti-cancer agents, the action of 4-(4-fluorophenyl)amino-5,6,7-trimethoxyquinazoline (compound 1018) on 10 different kinds of tumour cells were assayed by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide]. It possesses a broad spectrum of anti-cancer activity. The mechanism of action of 4-(4-fluorophenyl)amino-5,6,7-trimethoxyquinazoline (hereafter referred to as compound 1018) against tumour cells was studied in androgen-independent prostate cancer PC-3 cells by microscopic observation, LDH (lactate dehydrogenase) release assay and Western blotting. Its activity was dose-dependent, with an IC50 of 13.0±1.4 μM after 72 h treatment. Microscopy and LDH release assay indicated that the effect was through anti-proliferation rather than cytotoxicity. Western blot analysis also showed that treatment of cells with 50 μM compound 1018 for 30 min almost completely inhibited EGF (epidermal growth factor)-induced phosphorylation of ERK1/2 (extracellular-signal-regulated kinase 1/2), which suggests that its anti-proliferative effect is largely associated due to ERK1/2 activation being inhibited. Thus compound 1018 is a potential anti-cancer agent.
authors.affiliation: Department of Pharmacy, Bengbu Medical College, Anhui Engineering Technology Research Center of Biochemical Pharmaceuticals, Bengbu Anhui 233030, Peoples Republic of China.
authors.forename: Yinjiu
authors.initials: Y
authors.lastname: Huang
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.forename: Huazhang
authors.initials: H
authors.lastname: Wu
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011471:Prostatic Neoplasms; D011799:Quinazolines / Q000138:chemical synthesis / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C574936:4-(4-fluorophenyl)amino-5,6,7-trimethoxyquinazoline; D000970:Antineoplastic Agents; D011799:Quinazolines; D004815:Epidermal Growth Factor; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3