There is an increasing interest in developing novel eosinophil peroxidase (EPO) inhibitors, in order to provide new treatment strategies against chronic inflammatory and neurodegenerative diseases caused by eosinophilic disorder. Within this study, a ligand-based pharmacophore model for EPO inhibitors was generated and used for in silico screening of large 3 D molecular structure databases, containing more than 4 million compounds. Hits obtained were clustered and a total of 277 compounds were selected for biological assessment. A class of 2-(phenyl)amino-aceto-hydrazides with different substitution pattern on the aromatic ring was found to contain the most potent EPO inhibitors, exhibiting IC₅₀ values down to 10 nM. The generated pharmacophore model therefore, represents a valuable tool for the selection of compounds for biological testing. The compounds identified as potent EPO inhibitors will serve to initiate a hit to lead and lead optimisation program for the development of new therapeutics against eosinophilic disorders.

Hypericin, a tumour-selective photosensitizer, has shown potential in cancer therapy, but its poor water solubility has limited clinical use. To address this, we developed a water-soluble variant called high hypericin-loaded polyvinylpyrrolidone (HHL-PVP) to enhance hypericin's applicability, particularly for treating glioblastoma, a typically terminal disease. We tested HHL-PVP in both in vitro and in vivo models, first confirming its fluorescent properties in the lab and then assessing its efficacy in more complex animal models. Using subcutaneous and orthotopic tumour mouse models, we combined HHL-PVP administration with fluorescence-guided surgery and photodynamic therapy (PDT) to target residual tumour cells. Histological analysis of both healthy and tumour tissue showed HHL-PVP's over 97 % sensitivity and 100 % specificity in distinguishing tumour tissue. In subcutaneous glioblastoma models, significant tumour necrosis and remission occurred after HHL-PVP administration and a 20-minute white light application through the skin. These results highlight HHL-PVP's effectiveness in targeting and eradicating glioblastoma cells. Our findings provide strong evidence that HHL-PVP is a promising therapeutic option for glioblastoma, with its high sensitivity, specificity, and potential for tumour remission through PDT. This approach warrants further investigation in clinical trials and could improve outcomes for a disease that has been difficult to treat.

Background/Objectives: Curcumin is a food-grade (E100) photosensitiser with promising antimicrobial properties, but its applicability is limited due to low water-solubility. Complexation of curcumin with hydroxypropyl-γ-cyclodextrin (HP-γ-CD) overcomes this constraint and may facilitate using a single photosensitiser for Photodynamic Inactivation (PDI) of pathogens along the food-production chain and within a One Health framework. Methods: In this study, a novel method to complex HP-γ-CD and curcumin (abbreviated as CD-Cur) was developed and the compound was tested against Escherichia coli, Salmonella enterica, and Candidozyma auris, in liquid culture and in situ on abiotic surfaces, food matrices, and a porcine skin model. Results: Planktonic experiments demonstrated concentration-dependent PDI efficacy with photokilling exceeding the 3 log₁₀ threshold for all tested organisms at CD-Cur concentrations between 10 and 50 µM, illuminated with 435 nm (50 J/cm²) LED light, while dark and light toxicity remained below microbiologically relevant levels. CD-Cur induced high reductions of viable E. coli on food-contact plastic foil (3.35 log₁₀, 100 µM, white light, 100 J/cm²) and on abiotic surfaces (5.17–5.50 log₁₀, 30 µM, 435 nm, 25 J/cm²) with visible photobleaching of the photosensitiser after illumination. On salmon and pistachios, matrix-dependent effects were observed, but PDI still achieved practically relevant reductions (2.25–3.52 log₁₀, 30 µM, 435 nm, 200 J/cm²) of S. enterica without visible colour alteration of the food. In a porcine skin model, CD-Cur in a 1% hydroxyethyl cellulose hydrogel reduced C. auris contamination notably. The addition of 2 mM EDTA further enhanced antifungal effects, indicating that CD-Cur can also be applied in a medical context as topical application on porcine skin (2.41 log₁₀, 500 µM, 435 nm, 75 J/cm²). Conclusions: Together, these results show that a single, photodynamic system based on food-grade CD-Cur can provide broad antimicrobial efficacy across diverse matrices and pathogens in a One Health context.