Discovery of new HER2/EGFR dual kinase inhibitors based on the anilinoquinazoline scaffold as potential anti-cancer agents

Sadek M.M.Serrya R.A.Kafafy A.-H.N.Ahmed M.Wang F.Abouzid K.A.M.Department of Pharmaceutical Organic ChemistryFaculty of PharmacyMSA University6th OctoberCairoEgypt; Pharmaceutical Chemistry DepartmentFaculty of PharmacyAin Shams UniversityCairo 11566Egypt; Pharmaceutical Organic Chemistry DepartmentFaculty of PharmacyAssiut UniversityAbbassiaCairoEgypt; Chemistry LaboratoryFaculty of Life and Social SciencesSwinburne University of TechnologyMelbourneVICAustralia2020-01-092020-01-09201414756366https://doi.org/10.3109/14756366.2013.765417PubMed ID 23402383https://t.ly/zN55VScopusHerein, 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 ?M, respectively, and with IC50 equal to 3.98 and 1.04 ?M 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 ?M, respectively. � 2014 Informa UK Ltd. All rights reserved.EnglishAnilinoquinazolineEGFRHER2Kinase inhibitorsLapatinibantineoplastic agentepidermal growth factor receptorepidermal growth factor receptor 2molecular scaffoldphosphotransferase inhibitorquinazoline derivativestaurosporineantiproliferative activityarticlecancer cell culturedrug activitydrug designdrug synthesisenzyme inhibitionhumanIC 50molecular modelpriority journalAniline CompoundsAntineoplastic AgentsCell Line, TumorCell ProliferationCell SurvivalDrug DiscoveryHumansMolecular Docking SimulationMolecular StructureProtein Kinase InhibitorsQuinazolinesReceptor, Epidermal Growth FactorReceptor, erbB-2Discovery of new HER2/EGFR dual kinase inhibitors based on the anilinoquinazoline scaffold as potential anti-cancer agentsArticlehttps://doi.org/10.3109/14756366.2013.765417PubMed ID 23402383