8-Hydroxyquinoline (8-hq) exhibits potent antimicrobial activity against Staphylococcus aureus (SA) bacteria with MIC = 16.0–32.0 µM owing to its ability to chelate metal ions such as Mn²⁺, Zn^2+, and Cu²⁺ to disrupt metal homeostasis in bacterial cells. We demonstrate that Fe(8-hq)₃, the 1:3 complex formed between Fe(III) and 8-hq, can readily transport Fe(III) across the bacterial cell membrane and deliver iron into the bacterial cell, thus, harnessing a dual antimicrobial mechanism of action that combines the bactericidal activity of iron with the metal chelating effect of 8-hq to kill bacteria. As a result, the antimicrobial potency of Fe(8-hq)₃ is significantly enhanced in comparison with 8-hq. Resistance development by SA toward Fe(8-hq)₃ is considerably delayed as compared with ciprofloxacin and 8-hq. Fe(8-hq)₃ can also overcome the 8-hq and mupirocin resistance developed in the SA mutant and MRSA mutant bacteria, respectively. Fe(8-hq)₃ can stimulate M1-like macrophage polarization of RAW 264.7 cells to kill the SA internalized in such macrophages. Fe(8-hq)₃ exhibits a synergistic effect with both ciprofloxacin and imipenem, showing potential for combination therapies with topical and systemic antibiotics for more serious MRSA infections. The in vivo antimicrobial efficacy of a 2% Fe(8-hq)₃ topical ointment is confirmed by the use of a murine model with skin wound infection by bioluminescent SA with a reduction of the bacterial burden by 99 ± 0.5%, indicating that this non-antibiotic iron complex has therapeutic potential for skin and soft tissue infections (SSTIs).

Although iron is essential for all forms of life, it is also potentially toxic to cells as the increased and unregulated iron uptake can catalyze the Fenton reaction to produce reactive oxygen species (ROS), leading to lipid peroxidation of membranes, oxidation of proteins, cleavage of DNA and even activation of apoptotic cell death pathways. We demonstrate that Fe(hinok)₃ (hinok = 2-hydroxy-4-isopropyl-2,4,6-cycloheptatrien-1-one), a neutral Fe(III) complex with high lipophilicity is capable of bypassing the regulation of iron trafficking to disrupt cellular iron homeostasis; thus, harnessing remarkable anticancer activity against a panel of five different cell lines, including Pt-sensitive ovarian cancer cells (A2780; IC₅₀ = 2.05 ± 0.90 μM or 1.20 μg/mL), Pt-resistant ovarian cancer cells (A2780cis; IC₅₀ = 0.92 ± 0.73 μM or 0.50 μg/mL), ovarian cancer cells (SKOV-3; IC₅₀ = 1.23 ± 0.01 μM or 0.67 μg/mL), breast cancer cells (MDA-MB-231; IC₅₀ = 3.83 ± 0.12 μM or 2.0 μg/mL) and lung cancer cells (A549; IC₅₀ = 1.50 ± 0.32 μM or 0.82 μg/mL). Of great significance is that Fe(hinok)₃ exhibits unusual selectivity toward the normal HEK293 cells and the ability to overcome the Pt resistance in the Pt-resistant mutant ovarian cancer cells of A2780cis.

Background/Objectives: The widespread use of mupirocin and fusidic acid for the treatment and decolonization of Staphylococcus aureus (SA) skin infections has led to a rapid emergence of resistant strains, limiting the effectiveness of the few topical agents currently available for clinical use. Methods: In this study, we evaluate Fe(tropo)₃, a neutral and lipophilic iron(III)–tropolone complex, as a non-antibiotic topical antimicrobial candidate for the management of drug-resistant SA skin and soft tissue infections. Results: Fe(tropo)₃ exhibits potent in vitro activity against methicillin-susceptible SA, methicillin-resistant SA (MRSA), vancomycin-intermediate SA, and strains with high-level resistance to mupirocin and fusidate, with minimum inhibitory concentrations of 2 µg/mL across all tested isolates. The compound effectively penetrates bacterial cells, induces intracellular iron accumulation, and triggers dose-dependent reactive oxygen species generation, resulting in rapid bacterial killing and significant antibiofilm activity. Importantly, Fe(tropo)₃ shows a slower development of resistance compared with ciprofloxacin and displays synergistic activity with oxacillin against MRSA. When formulated as a 1% topical ointment, Fe(tropo)₃ significantly reduces bacterial burden in a murine excisional wound infection model, achieving a 98% ± 1% reduction in SA load without detectable hemolysis or skin irritation. Conclusions: These pilot study results support Fe(tropo)₃ as a clinically relevant, mechanism-distinct topical antimicrobial with potential utility in settings where resistance to existing topical antibiotics compromises standard care.

Lung cancer remains a leading cause of cancer-related mortality worldwide, underscoring the need for safer and more effective therapeutic strategies. In this study, zinc oxide nanoparticles (ZnO NPs) were synthesized via a green, biogenic approach using Lantana camara L. flower aqueous extract and evaluated for their anticancer potential against human non-small cell lung cancer (NSCLC) NCI-H460 cells. The biosynthesized ZnO NPs were characterized using UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), Transmission electron microscopy (TEM), energy-dispersive X-ray analysis (EDX), X-ray diffraction (XRD) and particle size analysis, confirming the formation of nanocrystalline ZnO. LC-MS profiling of the Lantana camara flower extract revealed the presence of several bioactive phytochemicals, including phenolic compounds, terpenoids, fatty acids, and alkaloids, which may contribute to the reduction and stabilization of ZnO NPs during green synthesis. Cytotoxicity assessment of ZnO NPs using MTT and trypan blue exclusion assays revealed a dose-dependent reduction in cell viability, with an IC₅₀ value of 50 µg/mL. Mechanistic investigations demonstrated that ZnO NP exposure induced significant oxidative stress, evidenced by increased nitric oxide, lipid peroxidation, and reactive oxygen species levels, along with depletion of intracellular glutathione. Apoptotic cell death was further confirmed by nuclear DNA fragmentation, mitochondrial membrane depolarization, and G0/G1 phase cell cycle arrest. Quantitative real-time PCR analysis revealed upregulation of the pro-apoptotic genes Bax and p53, accompanied by downregulation of the anti-apoptotic gene Bcl-2, indicating activation of a mitochondrial-dependent intrinsic apoptotic pathway. Collectively, these findings suggest that Lantana camara L. flower-mediated ZnO nanoparticles induced apoptotic responses associated with oxidative stress in NSCLC cells, highlighting their ability as an eco-friendly nanoplatform for further anticancer investigations.