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.

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.

Background/Objectives: Silver has long been used in medicine for its diverse effects. Coordination of this metal ion with bioactive ligands such as thiosalicylic acid derivatives allows the synthesis of potentially promising antimicrobial and antitumor agents. Methods: The in vitro antimicrobial activity of silver(I) complexes (C1–C5) and their corresponding ligands (L1–L5) was determined using a resazurin-based microdilution method, while the inhibition of preformed biofilms was assessed against S. aureus, P. mirabilis, and P. aeruginosa. To explore the binding modes and affinity of the investigated silver(I) complexes, a molecular docking study was performed against the LasR transcriptional regulator, while in silico ADMET screening was conducted using the pkCSM online platform. Finally, the evaluation of in vitro immunomodulatory effects of the silver(I) complexes was assessed by measuring cytokine concentrations and performing flow cytometry. Results: In vitro and in silico evaluations confirm that the C2 complex possesses an optimal structural balance of size and hydrophobicity, enabling superior antimicrobial and antibiofilm activity against P. aeruginosa. Regarding the immune response, treatment with the C3 complex decreased the concentrations of the proinflammatory cytokines IL-1β, TNF-α, IL-6, and IL-12, while increasing the concentration of the anti-inflammatory cytokine IL-10 after LPS stimulation. Conclusions: Our findings demonstrate that C2 primarily targets bacterial pathogens, while C3 exerts potent immunomodulatory and anti-inflammatory effects that differ between innate and acquired, naïve and primed immune system cells. Therefore, investigating the combined or sequential application of C2 and C3 may provide a promising strategy for the treatment of chronic biofilm-associated infections.

Background/Objectives: Inflammation plays a role at multiple levels, contributing to tumorigenesis, cellular proliferation, cell survival, and metastasis. The established link between chronic inflammation and tumor development has shifted the therapeutic focus toward nonsteroidal anti-inflammatory drugs, which exert their effects primarily through cyclooxygenase inhibition. Methods: In the present study, the antitumor potential of novel synthesized oxaprozin derivatives was evaluated using the MTT assay. The immunomodulatory effects of the selected derivative were determined in vitro by measuring cytokine concentrations and performing flow cytometry. To investigate the inhibitory capacity of these derivatives against cyclooxygenase enzymes, an in vitro inhibition assay was conducted using fluorometric screening kits, followed by in silico validation. Results: All tested tumor cell lines exhibited sensitivity to compound 1, which demonstrated the lowest cytotoxic effect against non-cancerous mMSCs and MRC-5 cells. This compound can effectively target tumor cells, inducing potent apoptosis in 4T1 breast cancer cells through a strategic shift in the Bax/Bcl-2 balance and the downregulation of the oncogenic driver Bcl-6. Although the synthesized oxaprozin derivatives showed moderate affinity for COX-1, none of the newly synthesized compounds achieved more than 50% inhibition against COX-2 at a concentration of 100 μM. Consistently, in silico procedures validated the results of the in vitro COX inhibition assay. Conclusions: The findings of this study indicate that compound 1 has the ability to modulate immune responses under stimulated conditions, and its potent antitumor activity may not be directly related to cyclooxygenase inhibition, suggesting the involvement of COX-independent pathways.