RT Journal Article
T1 Design, synthesis, HER2 inhibition and anticancer evaluation of new substituted 1,5-dihydro-4,1-benzoxazepines
A1 Cruz-López, Olga
A1 Ner, Matilde
A1 Nerín-Fonz, Francho
A1 Jiménez-Martínez, Yaiza
A1 Araripe, David
A1 Marchal, Juan A.
A1 Boulaiz, Houria
A1 Gutiérrez-de-Terán, Hugo
A1 Campos, Joaquín M.
A1 Conejo-García, Ana
K1 Antitumour
K1 Pyroptosis
K1 HER2
K1 Receptor
K1 Molecular modelling
K1 Benzoxazepines
K1 Cancer cell line
K1 Antineoplásicos
K1 Piroptosis
K1 Genes erbB-2
K1 Modelos moleculares
K1 Línea celular tumoral
AB 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 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.
PB Taylor & Francis
SN 1475-6366
YR 2021
FD 2021-07-12
LK http://hdl.handle.net/10668/4437
UL http://hdl.handle.net/10668/4437
LA en
NO Cruz-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):1553-1563
DS RISalud
RD Apr 10, 2025