Novel Copper(II) Complexes Containing β-Diketones and Imines as Ligands Modulate the Expression of lncRNAs in Triple-Negative Breast Cancer Cells

In this study, four novel Cu-(II) complexes of the type [Cu-(imine)-(b-diketone)-(NO₃)], namely, [Cu-(clmp)-(bta)-(NO₃)]·H₂O <b>1</b>, [Cu-(clmp)-(btacl)-(NO₃)] <b>2</b>, [Cu-(memp)-(bta)-(NO₃)]·H₂O <b>3</b>, and [Cu-(memp)-(btacl)-(NO₃)]·H₂O <b>4</b>, in which clmp = 4-chloro-<i>N</i>-(pyridin-2-methylene) aniline, memp = 4-methyl-<i>N</i>-(pyridin-2-methylene) aniline, bta = (4,4,4-trifluoro-1-phenyl-1,3-butanedionate, and btacl = 1-(4-chlorophenyl)-4,4,4-trifluoro-1,3-butanedionate), were prepared and characterized by elemental analysis, mass spectrometry, conductivity measurements, FT-IR, UV-vis, and single-crystal X-ray diffraction. The spectral and structural data confirmed that the β-diketone anions coordinate to Cu-(II) via the oxygen atoms, while the imine ligands coordinate by the nitrogen atoms. A weakly coordinated nitrate completes the coordination sphere around the metal center. Subsequently, <i>in vitro</i> experiments were conducted in MDA-MB231 triple-negative breast cancer cells (TNBC) in which MTT, SRB, LDH, clonogenicity, migration, and caspase activity analyses were performed. lncRNAs associated with epithelial-mesenchymal transition (EMT) were also quantified by qPCR. In the MTT assay, complexes <b>2</b> and <b>3</b> exhibited IC₅₀ values below 20 μM and greater selectivity toward the nontumorigenic MCF-10A cells. The SRB and LDH assays also demonstrated reduced cell viability and increased lactate dehydrogenase release mediated by both complexes. Clonogenicity and migration of TNBC cells were also reduced by <b>2</b> and <b>3</b>, and an increase in the activity of caspases 3 and 8 was observed, with the most pronounced effects recorded for <b>3</b>. Finally, the expression of lncRNAs was downregulated by <b>2</b> and <b>3</b>, demonstrating the role of the complexes in the modulation of EMT. These findings highlight complexes <b>2</b> and <b>3</b> as potential antitumor agents for TNBC, emphasizing the importance of exploring the intrinsic mechanisms underlying their anticancer activity.