title: Discovery of new HER2/EGFR dual kinase inhibitors based on the anilinoquinazoline scaffold as potential anti-cancer agents.
abstract: Herein, we designed and synthesized certain anilinoquinazoline derivatives bearing bulky arylpyridinyl, arylpropenoyl and arylpyrazolyl moieties at the 4' position of the anilinoquinazoline, as potential dual HER2/EGFR kinase inhibitors. A detailed molecular modeling study was performed by docking the synthesized compounds in the active site of the epidermal growth factor receptor (EGFR). The synthesized compounds were further tested for their inhibitory activity on EGFR and HER2 tyrosine kinases. The aryl 2-imino-1,2-dihydropyridine derivatives 5d and 5e displayed the most potent inhibitory activity on EGFR with IC50 equal to 2.09 and 1.94 μM, respectively, and with IC50 equal to 3.98 and 1.04 μM on HER2, respectively. Furthermore, the anti-proliferative activity of these most active compounds on MDA-MB-231 breast cancer cell lines, known to overexpress EGFR, showed an IC50 range of 2.4 and 2.5 μM, respectively.
authors: Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, MSA University , 6th October, Cairo , Egypt .
authors: Maiada M
authors: MM
authors: Sadek
authors: Rabah A
authors: RA
authors: Serrya
authors: Abdel-Hamid N
authors: AH
authors: Kafafy
authors: Marawan
authors: M
authors: Ahmed
authors: Feng
authors: F
authors: Wang
authors: Khaled A M
authors: KA
authors: Abouzid
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D055808:Drug Discovery; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000814:Aniline Compounds; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C512478:EGFR protein, human; C508053:ERBB2 protein, human