Copper transporter 1 affinity as a delivery strategy to improve the cytotoxic profile of rationally designed copper(II) complexes for cancer treatment.

Cisplatin is widely used to treat different types of cancer, but its severe side effects are the major disadvantage of this treatment. Therefore, other metals are currently the subject of research in the rational development of anticancer drugs, such as copper, that has been demonstrated to be promising in this scenario. Here, we evaluated the effects of two novel copper complexes against breast cancer cell lines, and also examined the influence of overexpressing copper transporter 1 (CTR1) on the cytotoxicity of these complexes. Complex (1) [Cu(sdmx-)2(phen)] showed low IC50 values, induced intense cell morphological changes and arrested the cell cycle at the sub-G1 phase in cancer cells. Complex (1) was tested in transfected cells overexpressing the CTR1 receptor in order to compare its steric effects with a less bulky ligand and more labile complex (2) [CuCl2(impy)]. A significant reduction of IC50 value was observed in CTR1 overexpressing cells for complex (2) (32 µM to 20 µM) as compared to (1) (2.78 µM to 3.41 µM), evidencing a possible uptake through copper reduction (Cu+2 â†’ Cu+1) mediated by CTR1. Thus, considering that CTR1 is a mediator of metallodrugs uptake, the development of strategies that use rational drug design is important in order to improve the therapeutic efficacy through greater specificity and consecutive reduction of side effects. Here we show the example for the case of copper(II) complexes.

N,N',N'' versus N,N',O imine-containing coordination motifs: ligand-directed synthesis of mononuclear and binuclear CuII compounds.

It is demonstrated here that tridentate imine ligands can control the nuclearity of copper(II) complexes based on the donor atoms present in the ligand. The N,N',N''-donating imine ligand led to a mononuclear compound, namely di-chlorido-[N,N-dimethyl-N'-(pyridin-2-yl-methyl-idene)ethane-1,2-di-amine]copper(II) monohydrate, [CuCl2(C10H15N3)]·H2O, 1, while the N,N',O-donating imine ligand produced a binuclear metal complex, namely µ2-chlorido-di-chlorido-(µ2-2-{[2-(di-methyl-amino)-ethyl]imino-methyl}phenolato)(N,N-dimethyl-ethylene-di-amine)-dicopper(II) 0.11-hydrate, [Cu2(C11H15N2O)Cl3(C4H12N2)]·0.11H2O, 2. The structure of 2 is a remarkable example of a binuclear copper(II) complex containing a single substituted 2-imino-methyl-phenolate ligand that has two copper(II) sites in square-pyramidal coordination.

Synthesis and crystal structure of di-chlorido-(1,10-phenanthroline-κ2N,N')gold(III) hexa-fluorido-phosphate.

A gold(III) salt of composition [AuCl2(C12H8N2)]PF6 was prepared and characterized by elemental and mass spectrometric analysis (ESI(+)-QTOF-MS), 1H nuclear magnetic resonance measurements and by single-crystal X-ray diffraction. The square-planar coordination sphere of AuIII comprises the bidentate 1,10-phenanthroline ligand and two chloride ions, with the AuIII ion only slightly shifted from the least-squares plane of the ligating atoms (r.m.s. = 0.018 Å). In contrast to two other previously reported AuIII-phenantroline structures that are stabilized by inter-actions involving the chlorido ligands, the packing of the title compound does not present these features. Instead, the hexa-fluorido-phosphate counter-ion gives rise to anion⋯π inter-actions that are a crucial factor for the crystal packing.