title: Design, synthesis and in vitro antitumor activity of 4-aminoquinoline and 4-aminoquinazoline derivatives targeting EGFR tyrosine kinase.
abstract: Two series of new 6-alkoxy-4-substituted-aminoquinazolines (2-4f) and their bioisoteric quinoline congeners (5-7c) were designed and synthesized. Virtual screening was carried out through docking the designed compounds into the ATP binding site of epidermal growth factor receptor (EGFR) to predict if these compounds have analogous binding mode to the EGFR inhibitors. The newly synthesized compounds were tested in vitro on human breast carcinoma cell line (MCF-7) in which EGFR is highly expressed. Most of the tested compounds exploited potent antitumor activity with IC(50) values in the nanomolar range in particular compound 3b which displayed the highest activity among the tested compounds with IC(50) equal to 0.13 nmol.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, Abbasia, Cairo 11566, Egypt. abouzid@yahoo.com
authors.forename: Khaled
authors.initials: K
authors.lastname: Abouzid
authors.forename: Samia
authors.initials: S
authors.lastname: Shouman
mesh_terms: D000634:Aminoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D008958:Models, Molecular; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000634:Aminoquinolines; D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors