The DNA and bovine serum albumin binding evaluation of the dinuclear platinum(II) complex, [{PtCl(NH3)2}2(?-1,5-nphe)](ClO4)2 (1,5-nphe is the bridging 1,5-naphthyridine ligand) was investigated by UV?Vis and fluorescence emission spectroscopy. Influence of platinum(II) complex on immune response was also estimated. Peritoneal splenocytes isolated from BALB/c mice were treated with Concanavalin A (ConA) and platinum(II) complex. Concentrations of IFN-?, IL-1?, IL-17, TNF-? and IL-10 were measured and immunophenotyping was performed. Results showed notable immunomodulatory effects. Pt(II) complex has an inhibitory effect on the release of proinflammatory cytokines in ConA activated splenocytes and CD3+ T cells.

Many complexes have shown antitumor potential, including the bis(S-ethyl-2-thiosalicylate)palladium(II) complex. The aim of this study was to investigate potential immunomodulatory effects of this complex on acquired and innate immunity, in vitro. The effect was assessed based on the levels of cytokines tumor necrosis factor alpha (TNF-α), interleukin (IL) 1β, interferon gamma (IFN-γ), IL-17 and IL-10. Cytokine concentrations were measured by ELISA assay. Pd(II) complex led to a reduced secretion of most pro-inflammatory cytokines. The effects of the complex were more intense in non-activated cells. The same effect was shown in cells of acquired and innate immunity. These effects make the Pd(II) complex not only a potential antitumor agent, but also an anti-inflammatory agent.

The knowledge of the essential role of copper in the human body, especially in its involvement in various important metalloenzymes, such as cytochrome c oxidase, copper-zinc superoxide dismutase, tyrosinase, lysyl oxidase and other, has greatly stimulated research interest in copper coordination compounds from both chemical and medicinal perspectives. Dinuclear copper complexes, in particular, have shown considerable therapeutic potential, as the unique combination of copper chemistry and dinuclear structural modifications has given rise to various highly bioactive compounds and new medicinal possibilities. In this paper, biological activities of medicinally attractive homodinuclear and heterodinuclear copper complexes are reviewed and their therapeutic potential and future perspectives are discussed. An in-depth analysis of key elements that impact their structure-activity relationships was performed and through a rational design approach, supported by the available literature, concluding remarks were given, that could possibly lead to more optimal therapeutic dinuclear copper complex structures. Known limitations regarding copper toxicity, bioavailability, metabolism and clearance were analyzed and possible strategies to mitigate them were discussed as well, including the possibe use of dinuclear copper complexes in targeted therapy and stimuli-responsive drug delivery systems. Finally, the prospects of using dinuclear copper complexes in personalized or combination therapy are postulated.

New copper(II) (C1) and palladium(II) (C2) complexes with S,O-tetradentate ligand (L) derived from thiosalicylic and thiopropionic acids were synthesized. In cell-based assays, (C1) exhibited the most pronounced activity within the tested compound series and was therefore advanced for mechanistic evaluation in 4T1 triple-negative breast cancer cells. (C1) significantly reduced 4T1 cell viability by inducing early and late apoptosis, accompanied by mitochondrial membrane depolarization and enhanced cytochrome C release. Consistently, (C1) increased the Bax/Bcl-2 ratio, promoting a pro-apoptotic shift. In parallel, (C1) triggered autophagy, as evidenced by decreased p62 and LC3B levels, induced G0/G1 cell-cycle arrest, and suppressed proliferative signaling by downregulating Ki67, cyclin D, and phosphorylated AKT. The DNA-binding studies showed moderate to strong affinity, favoring minor groove binding, with higher affinity for (C1) than for (C2). Tryptophan fluorescence quenching indicated a strong interaction with BSA via a predominantly static mechanism, more pronounced for (C1). Molecular docking at the DNA and BSA binding sites corroborated experimental findings and suggested favorable interactions between the complexes and apoptosis-related proteins (CASP3, BAX, and BCL2). The integrated experimental and computational data identify (C1) as a biologically active compound with multimodal biological effects in vitro, supporting further structural optimization and mechanistic investigation.