Effects on estrogen-dependent and triple negative breast cancer cells growth of Ni(II), Zn(II) and Cd(II) complexes with the Schiff base derived from pyridine-2-carboxaldehyde and 5,6-diamino-1,3-dimethyluracil explored through the renin-angiotensin system (RAS)-regulating aminopeptidases

• Published in: Journal of inorganic biochemistry 2018-08, Vol.185, p.52-62
• Main Authors: Illán-Cabeza, Nuria A., Jiménez-Pulido, Sonia B., Hueso-Ureña, Francisco, Ramírez-Expósito, María J., Sánchez-Sánchez, Purificación, Martínez-Martos, José M., Moreno-Carretero, Miguel N.
• Format: Article
• Language: English
• Subjects: Aldehydes - chemistry; Aminopeptidases - metabolism; Breast Neoplasms - enzymology; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Breast tumors; Cadmium - chemistry; Cell Line, Tumor; Cell Proliferation; Crystal structure; Crystallography, X-Ray; Estrogens - metabolism; Humans; Molecular Structure; Neoplasms, Hormone-Dependent - enzymology; Neoplasms, Hormone-Dependent - metabolism; Neoplasms, Hormone-Dependent - pathology; Nickel - chemistry; Pyridimines; Pyridines - chemistry; Renin-Angiotensin System; Schiff Bases - chemistry; Triple Negative Breast Neoplasms - enzymology; Triple Negative Breast Neoplasms - metabolism; Triple Negative Breast Neoplasms - pathology; Uracil - analogs & derivatives; Uracil - chemistry; Zinc - chemistry
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2018.04.022

A series of Ni(II), Zn(II) and Cd(II) complexes with the Schiff base derived from the condensation 1:1 from pyridine-2-carboxaldehyde and 5,6-diamino-1,3-dimethyluracil (6-amino-1,3-dimethyl-5-[(pyridin-2-ylmethylidene)-amino]pyrimidine-2,4(1H,3H)-dione, DAAUPic) were synthesized and subsequently characterized by means of elemental analysis, FT-IR, NMR and nine of them by X-ray diffraction. Except the [Zn(μ-O,O′-AcO)(N5,N6,N1F-DAAUPicH–1)]2 and [Cd(O,O′-NO3)(μ-O4,(N5,N6,N1F)-DAAUPicH−1)(H2O)]2·2H2O dimers and the [Cd(μ-S,N-SCN)(N5,N6,N1F-DAAUPicH−1)]n chain-like polymer, all of them display monomeric molecular structures. The anticancer activity of compounds was also explored studying their effects on renin-angiotensin system (RAS)-regulating aminopeptidases on estrogen-dependent and triple negative breast cancer cell lines. At the concentrations used, some of the complexes showed different effects on (RAS) peptidases, which support the idea that their effects on cell growth/proliferation could be related to autocrine/paracrine regulatory functions of their corresponding peptide substrates. Eleven Ni(II), Zn(II) and Cd(II) complexes with the Schiff base derived from the condensation 1:1 from pyridine-2-carboxaldehyde and 5,6-diamino-1,3-dimethyluracil have been characterized. The antitumor activity against human estrogen receptor (ER)-positive MCF-7 and triple negative MDA-MB-231 breast cancer cells were investigated testing their effects on (renin-angiotensin system)-regulating aminopeptidase specific activities. [Display omitted] •Eleven Ni2+, Zn2+ and Cd2+ complexes with a uracil Schiff base have been synthetized.•The crystal structures of nine complexes have been determined.•Compounds were tested with estrogen-dependent and triple-negative breast cancer cells.•Complexes act through specific mechanisms of cell functions in which RAS is involved.