Gold(i/iii) complexes based on the marine natural betaine norzooanemonin display excellent antibacterial and cyctotoxic activity based on the nature of carboxylate functionalization.

Silver N‐heterocyclic carbene (NHC) complexes are known to form biscarbene species from monocarbene analogs in protic polar solvents. However, the effect of the respective species of silver NHC complexes on their biological activity against bacteria or cancer cells has not been systematically explored, either in vitro or in vivo. The direct and simple conversion of monocarbene silver N‐heterocyclic carbene (NHC) halide complexes (NHC)AgX, (X=Cl, Br) 1 a/b–5 a/b to their biscarbene analogues (NHC)₂AgX 1 c/d–5 c/d is reported. The biscarbenes demonstrated generally lower activity against bacteria compared to the monocarbene complexes; however, both types showed similar activity against tumor cells and a non‐tumor reference cell line. Selected mono‐ and biscarbene complexes 3 a and 3 c showed similar strong inhibitory effects on thioredoxin reductase in vitro and in cellulo and had a similar level of metal uptake into A549 cells. The subsequent evaluation of their effects in vivo revealed relatively low toxicity and high antitumoral efficacy of both selected complexes in mice. The biscarbene silver organometallic 3 c showed the most pronounced reduction of tumor growth in animals. The results indicate that both (NHC)AgX and (NHC)₂AgX complexes could trigger their anticancer activity as biscarbene complexes, making this the preferred form for future anticancer metallodrug development.

The antibacterial properties of Ag(I) coordination compounds are well documented; however, their effectiveness is highly dependent on the choice of appropriate ligands, and it is frequently hindered by their low water solubility and limited bioavailability. Herein, six new Ag(I) complexes incorporating the quinazolinone thioamide mqztH (=2-mercapto-4(3H)-quinazolinone) and phosphine co-ligands were synthesized and investigated for their antibacterial activity. In vitro activity assays against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacterial strains revealed that all complexes selectively inhibited S. aureus bacterial growth. Structure–activity relationship analysis showed that monodentate PPh₃ co-ligands play a key role in enhancing the antibacterial efficacy of their complexes. Notably, complex [AgCl(mqztH)(PPh₃)₂] (1) exhibited broad-spectrum activity, with IC₅₀ values of 4.2 ± 1.4 μg mL⁻¹ (4.9 μΜ) for S. aureus and 63 ± 1.9 μg mL⁻¹ (75 μΜ) for E. coli bacteria. To improve solubility and antibacterial activity, complex 1 was encapsulated in barium alginate (BaAlg) matrices to form hydrogel-based drug delivery formulations [1]@BaAlg. The synthesized formulations retained the bactericidal effect of the complex, achieving comparable activity at concentrations lower by an order of magnitude compared to complex 1 in free form. Combined with the demonstrated high biocompatibility of complex 1 toward L929 normal eukaryotic cells, as well as the biocompatible nature of the alginate matrix, these findings underscore the strong potential of the complex 1-loaded hydrogel formulations for further investigation and development as effective antibacterial drug platforms. Mechanistic studies confirmed the redox-active nature of complex 1 and its potential to inhibit the function of glutathione reductase (GR) and thioredoxin reductase (TrxR) at low concentrations, suggesting the interference with bacterial redox homeostasis as a relevant mechanism of bioactivity.

We report a new chelating pyridyl–imine ligand bearing a riboflavin-derived pendant group and its Pt(II) complexes 1 and 2, designed as cisplatin- and oxaliplatin-like derivatives. Both complexes reacted with DNA and a histone-derived peptide, with 1 showing markedly higher covalent reactivity. However, this trend was not reflected in biological activity. Complex 2 displayed micromolar antiproliferative effects and pronounced antibacterial activity, particularly against Bacillus subtilis, whereas 1 was inactive in the tested models. Cellular accumulation studies excluded enhanced Pt uptake as the origin of this difference. Fluorescence microscopy performed on Escherichia Coli and Bacillus subtilis indicated that 2 affects bacterial DNA and membrane potential, consistent with a dual antibacterial mechanism. Comparison with oxaliplatin and the free flavin ligands showed that both the Pt–oxalate fragment and the riboflavin-containing ligand are required for activity.