Silver(I) Complexes with Thiosalicylic Acid Derivatives as Promising Antimicrobial, Antibiofilm, and Immunomodulatory Agents

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.