Novel thienopyrimidine derivatives as dual EGFR and VEGFR-2 inhibitors: design, synthesis, anticancer activity and effect on cell cycle profile

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dc.AffiliationOctober University for modern sciences and Arts (MSA)
dc.contributor.authorMghwary A.E.-S.
dc.contributor.authorGedawy E.M.
dc.contributor.authorKamal A.M.
dc.contributor.authorAbuel-Maaty S.M.
dc.contributor.otherDepartment of Pharmaceutical Organic Chemistry
dc.contributor.otherFaculty of Pharmacy
dc.contributor.otherCairo University
dc.contributor.otherCairo
dc.contributor.otherEgypt; Department of Pharmaceutical Chemistry
dc.contributor.otherFaculty of Pharmacy and Pharmaceutical Industries
dc.contributor.otherBadr University in Cairo BUC
dc.contributor.otherCairo
dc.contributor.otherEgypt; Department of Organic Chemistry
dc.contributor.otherFaculty of Pharmacy
dc.contributor.otherOctober University for Modern Science and Arts (MSA)
dc.contributor.otherCairo
dc.contributor.otherEgypt
dc.date.accessioned2020-01-09T20:40:43Z
dc.date.available2020-01-09T20:40:43Z
dc.date.issued2019
dc.descriptionScopus
dc.description.abstractAim: Design and synthesis of thienopyrimidine derivatives as dual EGFR and VEGFR-2 inhibitors.Material and methods: A series of novel 6,7,8,9-tetrahydro-5H-cyclohepta[4,5]thieno[2,3-d]pyrimidine derivatives with different substituents on C-4 position was synthesized and evaluated for their anticancer activity against MCF-7 cell line. EGFR, VEGFR-2 inhibitory assay, the cell cycle analysis and apoptosis induction ability of the most potent compound 5f were evaluated.Results: Most of the compounds showed moderate to significant anticancer activity. Compound 5f exhibited the most potent anticancer activity being 1.73- and 4.64-folds more potent than erlotinib and doxorubicin, respectively. Compound 5f showed potent EGFR inhibitory activity being 1.18-folds more potent than reference standard erlotinib and it also showed good VEGFR-2 inhibitory activity at the micromolar level with IC 50 value 1.23��M. Compound 5f caused induction of cell cycle arrest at G2/M phase and accumulation of cells in pre-G1 phase. Compound 5f induced cellular apoptosis. � 2019, � 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.en_US
dc.description.urihttps://www.scimagojr.com/journalsearch.php?q=17605&tip=sid&clean=0
dc.identifier.doihttps://doi.org/10.1080/14756366.2019.1593160
dc.identifier.doiPubMed ID 30919701
dc.identifier.issn14756366
dc.identifier.otherhttps://doi.org/10.1080/14756366.2019.1593160
dc.identifier.otherPubMed ID 30919701
dc.identifier.urihttps://t.ly/y6MXy
dc.language.isoEnglishen_US
dc.publisherTaylor and Francis Ltden_US
dc.relation.ispartofseriesJournal of Enzyme Inhibition and Medicinal Chemistry
dc.relation.ispartofseries34
dc.subjectanticancer activityen_US
dc.subjectapoptosisen_US
dc.subjectdesignen_US
dc.subjectEGFRen_US
dc.subjectsynthesisen_US
dc.subjectThieno[2,3-d]pyrimidinesen_US
dc.subjectvandetaniben_US
dc.subjectVEGFR-2en_US
dc.subject3 [(6,7,8,9 tetrahydro 5h cyclohepta[4,5]thieno[2,3 d]pyrimidin 4 yl)oxy]anilineen_US
dc.subject4 (2 chlorophenoxy) 6,7,8,9 tetrahydro 5h cyclohepta[4,5]thieno[2,3 d]pyrimidineen_US
dc.subject4 (4 bromophenoxy) 6,7,8,9 tetrahydro 5h cyclohepta[4,5]thieno[2,3 d]pyrimidineen_US
dc.subject4 (4 chloro 3 methylphenoxy) 6,7,8,9 tetrahydro 5h cyclohepta[4,5]thieno[2,3 d]pyrimidineen_US
dc.subject4 (4 chlorophenoxy) 6,7,8,9 tetrahydro 5h cyclohepta[4,5]thieno[2,3 d]pyrimidineen_US
dc.subject4 (4 fluorophenoxy) 6,7,8,9 tetrahydro 5h cyclohepta[4,5]thieno[2,3 d]pyrimidineen_US
dc.subject4 (4 methoxyphenoxy) 6,7,8,9 tetrahydro 5h cyclohepta[4,5]thieno[2,3 d]pyrimidineen_US
dc.subject4 (4 nitrophenoxy) 6,7,8,9 tetrahydro 5h cyclohepta[4,5]thieno[2,3 d]pyrimidineen_US
dc.subject4 (4 tolyloxy) 6,7,8,9 tetrahydro 5h cyclohepta[4,5]thieno[2,3 d]pyrimidineen_US
dc.subject4 (o tolyloxy) 6,7,8,9 tetrahydro 5h cyclohepta[4,5]thieno[2,3 d]pyrimidineen_US
dc.subject4 [(6,7,8,9 tetrahydro 5h cyclohepta[4,5]thieno[2,3 d]pyrimidin 4 yl)amino]benzenesulfonamideen_US
dc.subject4 [(6,7,8,9 tetrahydro 5h cyclohepta[4,5]thieno[2,3 d]pyrimidin 4 yl)oxy]anilineen_US
dc.subjectantineoplastic agenten_US
dc.subjectdoxorubicinen_US
dc.subjectepidermal growth factor receptoren_US
dc.subjectepidermal growth factor receptor kinase inhibitoren_US
dc.subjecterlotiniben_US
dc.subjectgefitiniben_US
dc.subjectlapatiniben_US
dc.subjectn (4 methylpyrimidin 2 yl) 4 [(6,7,8,9 tetrahydro 5h cyclohepta[4,5]thieno[2,3 d]pyrimidin 4 yl)amino]benzenesulfonamideen_US
dc.subjectn (pyrimidin 2 yl) 4 [(6,7,8,9 tetrahydro 5h cyclohepta[4,5] thieno[2,3 d]pyrimidin 4 yl)amino]benzenesulfonamideen_US
dc.subjectpyrimidine derivativeen_US
dc.subjectunclassified drugen_US
dc.subjectvandetaniben_US
dc.subjectvasculotropin receptor 2en_US
dc.subjectvasculotropin receptor 2 inhibitoren_US
dc.subjectantineoplastic agenten_US
dc.subjectEGFR protein, humanen_US
dc.subjectepidermal growth factor receptoren_US
dc.subjectKDR protein, humanen_US
dc.subjectprotein kinase inhibitoren_US
dc.subjectpyrimidine derivativeen_US
dc.subjectthienopyrimidineen_US
dc.subjectvasculotropin receptor 2en_US
dc.subjectantineoplastic activityen_US
dc.subjectapoptosisen_US
dc.subjectArticleen_US
dc.subjectcarbon nuclear magnetic resonanceen_US
dc.subjectcell cycleen_US
dc.subjectcell cycle arresten_US
dc.subjectcell cycle G2 phaseen_US
dc.subjectcell cycle M phaseen_US
dc.subjectchlorinationen_US
dc.subjectcontrolled studyen_US
dc.subjectdrug designen_US
dc.subjectdrug synthesisen_US
dc.subjectelemental analysisen_US
dc.subjectenzyme inhibitionen_US
dc.subjectheatingen_US
dc.subjecthumanen_US
dc.subjecthuman cellen_US
dc.subjectIC50en_US
dc.subjectMCF-7 cell lineen_US
dc.subjectMTT assayen_US
dc.subjectnucleophilicityen_US
dc.subjectpriority journalen_US
dc.subjectproton nuclear magnetic resonanceen_US
dc.subjectreaction analysisen_US
dc.subjectsubstitution reactionen_US
dc.subjectantagonists and inhibitorsen_US
dc.subjectcell cycleen_US
dc.subjectcell proliferationen_US
dc.subjectchemical structureen_US
dc.subjectchemistryen_US
dc.subjectdose responseen_US
dc.subjectdrug effecten_US
dc.subjectdrug screeningen_US
dc.subjectmetabolismen_US
dc.subjectmolecular dockingen_US
dc.subjectstructure activity relationen_US
dc.subjectsynthesisen_US
dc.subjectAntineoplastic Agentsen_US
dc.subjectApoptosisen_US
dc.subjectCell Cycleen_US
dc.subjectCell Proliferationen_US
dc.subjectDose-Response Relationship, Drugen_US
dc.subjectDrug Screening Assays, Antitumoren_US
dc.subjectErbB Receptorsen_US
dc.subjectHumansen_US
dc.subjectMCF-7 Cellsen_US
dc.subjectMolecular Docking Simulationen_US
dc.subjectMolecular Structureen_US
dc.subjectProtein Kinase Inhibitorsen_US
dc.subjectPyrimidinesen_US
dc.subjectStructure-Activity Relationshipen_US
dc.subjectVascular Endothelial Growth Factor Receptor-2en_US
dc.titleNovel thienopyrimidine derivatives as dual EGFR and VEGFR-2 inhibitors: design, synthesis, anticancer activity and effect on cell cycle profileen_US
dc.typeArticleen_US
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