title: Synthesis and in vitro antitumor activities of novel 4-anilinoquinazoline derivatives.
abstract: A series of 6, 7-dialkoxy-4-anilinoquinazolines were designed, synthesized by substituting different heterocycles on 6-position and a variety of anilines on 4-position of the quinazoline. These novel quinazoline compounds were screened for their cytotoxic effect on epidermal growth factor receptor overexpressing skin epidermoid carcinoma cell line (A431), by using nonoverexpressing tumor cells as negative control (breast adeno carcinoma cell line MCF-7). 2-Butyl-4-chloro-1-{3-[7-methoxy-4-(3-(trifluoromethyl)phenylamino)quinazolin-6-yloxy]-propyl}-1H-imidazole-5-carboxaldehyde (30) and 2-butyl-4-chloro-1-{3-[4-(3-iodophenyl amino)-7-methoxyquinazolin-6-yloxy]propyl}-1H-imidazole-5-carboxaldehyde (33) were found to be more potent against A431 cell line (IC(50) 3.5 and 3 microM) and their activities are comparable to gefitinib. Insilico docking experiments with human EGFR Tyrosine kinase domain (PDB id-2gs2) indicated that 33 docks at the same position as that of gefitinib involving Val702, Ala719, Ser696, and Lys721.
authors.affiliation: Vittal Mallya Scientific Research Foundation, Bangalore, Karnataka, India.
authors.forename: Venkateshappa
authors.initials: V
authors.lastname: Chandregowda
authors.forename: A K
authors.initials: AK
authors.lastname: Kush
authors.forename: G
authors.initials: G
authors.lastname: Chandrasekara Reddy
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D066246:ErbB Receptors / Q000737:chemistry / Q000378:metabolism; D000077156:Gefitinib; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000473:pathology*; D010770:Phosphotransferases / Q000037:antagonists & inhibitors; D017434:Protein Structure, Tertiary; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000814:Aniline Compounds; D000970:Antineoplastic Agents; D011799:Quinazolines; D010770:Phosphotransferases; D066246:ErbB Receptors; D000077156:Gefitinib; C023650:aniline