Design, synthesis, HER2 inhibition and anticancer evaluation of new substituted 1,5-dihydro-4,1- benzoxazepines Cruz López, Olga María Ner, Matilde Jiménez Martínez, Yaiza Marchal Corrales, Juan Antonio Boulaiz Tassi, Houria Campos Rosa, Joaquín María Conejo García, Ana Antitumour Pyroptosis HER2 receptor Molecular modelling Benzoxazepines A. C. -G. is thankful to Consejeria de Economia, Conocimiento, Empresas y Universidad of the Junta de Andalucia (Excellence Research Project P18-RT-1679) and the Oficina de Transferencia de Resultados de Investigacion 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), Fundacion Mutua Madrilena (project FMM-AP16683-2017), Consejeria de Salud Junta de Andalucia (PI-0089-2017) for financial support. A 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 mM. 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 mM) does not produce any modification in the expression of pro-caspase 3, but increases the caspase 1 expression, and promotes pyroptosis. 2021-09-14T09:03:03Z 2021-09-14T09:03:03Z 2021-07-12 info:eu-repo/semantics/article Olga Cruz-López... [et al.] (2021) Design, synthesis, HER2 inhibition and anticancer evaluation of new substituted 1,5-dihydro-4,1-benzoxazepines, Journal of Enzyme Inhibition and Medicinal Chemistry, 36:1, 1553-1563, DOI: [10.1080/14756366.2021.1948841] http://hdl.handle.net/10481/70199 10.1080/14756366.2021.1948841 eng http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Atribución 3.0 España Taylor & Francis