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Design, synthesis, HER2 inhibition and anticancer evaluation of new substituted 1,5-dihydro-4,1-benzoxazepines

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dc.contributor.authorCruz-López, Olga
dc.contributor.authorNer, Matilde
dc.contributor.authorNerín-Fonz, Francho
dc.contributor.authorJiménez-Martínez, Yaiza
dc.contributor.authorAraripe, David
dc.contributor.authorMarchal, Juan A.
dc.contributor.authorBoulaiz, Houria
dc.contributor.authorGutiérrez-de-Terán, Hugo
dc.contributor.authorCampos, Joaquín M.
dc.contributor.authorConejo-García, Ana
dc.contributor.authoraffiliation[Cruz-López,O; Ner,M; Campos,JM; Conejo-García,A] Department of Medicinal and Organic Chemistry, Faculty of Pharmacy, University of Granada, Granada, Spain. [Cruz-López,O; Jiménez-Martínez,Y; Marchal,JA; Boulaiz,H; Campos,JM; Conejo-García,A] Biosanitary Institute of Granada (ibs.GRANADA), SAS-University of Granada, Granada, Spain. [Nerín-Fonz,F; Araripe,D; Gutiérrez-de-Terán,H] Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweeden. [Jiménez-Martínez,Y; Marchal,JA; Boulaiz,H] Biopathology and Medicine Regenerative Institute, University of Granada, Granada, Spain. [Jiménez-Martínez,Y; Marchal,JA; Boulaiz,H] Excellence Research Unit “Modeling Nature” (MNat), Department of Human Anatomy and Embryology, University of Granada, Granada, Spain.
dc.contributor.funderA. C. -G. is thankful to Consejería de Economía, Conocimiento, Empresas y Universidad of the Junta de Andalucía (Excellence Research Project P18-RT-1679) and the Oficina de Transferencia de Resultados de Investigación of the University of Granada (PR/17/006 project) for financial support. J. A. M. and H. B. thanks Instituto de Salud Carlos III (RTI2018-101309-B-C22), Fundación Mutua Madrileña (project FMM-AP16683-2017), Consejería de Salud Junta de Andalucía (PI-0089-2017) for financial support.
dc.date.accessioned2022-11-30T12:12:03Z
dc.date.available2022-11-30T12:12:03Z
dc.date.issued2021-07-12
dc.description.abstractA series of 11 new substituted 1,5-dihydro-4,1-benzoxazepine derivatives was synthesised to study the influence of the methyl group in the 1-(benzenesulphonyl) moiety, the replacement of the purine by the benzotriazole bioisosteric analogue, and the introduction of a bulky substituent at position 6 of the purine, on the biological effects. Their inhibition against isolated HER2 was studied and the structure-activity relationships have been confirmed by molecular modelling studies. The most potent compound against isolated HER2 is 9a with an IC50 of 7.31 µM. We have investigated the effects of the target compounds on cell proliferation. The most active compound (7c) against all the tumour cell lines studied (IC50 0.42-0.86 µM) does not produce any modification in the expression of pro-caspase 3, but increases the caspase 1 expression, and promotes pyroptosis.es_ES
dc.description.versionYeses_ES
dc.identifier.citationCruz-López O, Ner M, Nerín-Fonz F, Jiménez-Martínez Y, Araripe D, Marchal JA, et al. Design, synthesis, HER2 inhibition and anticancer evaluation of new substituted 1,5-dihydro-4,1-benzoxazepines. J Enzyme Inhib Med Chem. 2021 Dec;36(1):1553-1563es_ES
dc.identifier.doi10.1080/14756366.2021.1948841es_ES
dc.identifier.essn1475-6374
dc.identifier.issn1475-6366
dc.identifier.pmcPMC8279156
dc.identifier.pmid34251942es_ES
dc.identifier.urihttp://hdl.handle.net/10668/4437
dc.journal.titleJournal of Enzyme Inhibition and Medicinal Chemistry
dc.language.isoen
dc.page.number12 p.
dc.publisherTaylor & Francises_ES
dc.relation.publisherversionhttps://www.tandfonline.com/doi/full/10.1080/14756366.2021.1948841es_ES
dc.rightsAtribución 4.0 Internacional*
dc.rights.accessRightsAcceso abiertoes_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectAntitumoures_ES
dc.subjectPyroptosises_ES
dc.subjectHER2es_ES
dc.subjectReceptores_ES
dc.subjectMolecular modellinges_ES
dc.subjectBenzoxazepineses_ES
dc.subjectCancer cell linees_ES
dc.subjectAntineoplásicoses_ES
dc.subjectPiroptosises_ES
dc.subjectGenes erbB-2es_ES
dc.subjectModelos moleculareses_ES
dc.subjectLínea celular tumorales_ES
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agentses_ES
dc.subject.meshMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, Tumores_ES
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Growth Processes::Cell Proliferationes_ES
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Pharmacological Phenomena::Dose-Response Relationship, Druges_ES
dc.subject.meshMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Cytological Techniques::Drug Screening Assays, Antitumores_ES
dc.subject.meshMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humanses_ES
dc.subject.meshMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Models, Moleculares_ES
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Molecular Structurees_ES
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protein Kinase Inhibitorses_ES
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Tyrosine Kinases::Receptor Protein-Tyrosine Kinases::Receptor, erbB-2es_ES
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Structure-Activity Relationshipes_ES
dc.subject.meshMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Drug Discovery::Drug Designes_ES
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Peptide Hydrolases::Cysteine Proteases::Cysteine Endopeptidases::Caspases::Caspases, Effector::Caspase 3es_ES
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Peptide Hydrolases::Cysteine Proteases::Cysteine Endopeptidases::Caspases::Caspases, Initiator::Caspase 1es_ES
dc.subject.meshMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Toxicity Tests::Inhibitory Concentration 50es_ES
dc.titleDesign, synthesis, HER2 inhibition and anticancer evaluation of new substituted 1,5-dihydro-4,1-benzoxazepineses_ES
dc.typeresearch article
dc.type.hasVersionVoR
dspace.entity.typePublication

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