Remodelling of the extracellular matrix is associated with various disease processes, particularly tumorigenesis. A major part in this process is played by enzymes which catalyse the chemical modification or degradation of matrix proteins, which therefore represent biomolecular targets for both therapeutic intervention as well as for molecular imaging using radiolabelled molecules by positron emission tomography (PET) and single photon emission computed tomography (SPECT). With regards to the latter option of diagnostic targeting, cysteine cathepsins, lysyl oxidases and transglutaminase were taken into focus by us as targets for radiotracer development for functional tumour imaging by PET. While cysteine cathepsins represent prominent tumour-associated matrix-degrading proteases, lysyl oxidases and transglutaminase 2 mediate oxidative and transamidative cross-linking of extracellular proteins, respectively, with various additional intracellular enzymatic functions. After a short introduction into molecular imaging with special emphasis on the importance of PET in drug development and the function of the mentioned enzymes in tumour progression, the pursued strategies for ligand identification, labelling with suitable radionuclides and the results of radiopharmacological characterisation of the tracer compounds will be outlined.

Caspases, the family of cysteine aspartate specific proteases, are well known as killer enzymes driving cell death via apoptosis or pyroptosis. However, the latest findings on the caspases indicate important and non-lethal roles of these enzymes ranging from immune response, cell fate determination, cell proliferation and cellular remodeling. Caspase-3 is a key mediator of neuronal programmed cell death and plays an essential role in the development of the nervous system. Its activation is a feature of many chronic neurodegenerative diseases often characterized by perturbations in physiological synapses structure and function as in Alzheimer and Parkinson diseases. Therefore, these studies validate caspase-3 inhibitors as a novel pharmacological target against multiple diseases.

Many caspase-3 inhibitors have been developed but only few compounds have progressed in clinical trials. Novel, improved, brain penetrable compounds are urgently needed for developing new therapeutics for neurodegenerative pathologies. We have designed and synthesized via multicomponent reaction (MCR) a new non-covalent, non-peptidomimetic, and selective caspase-3 inhibitor.

The results of the biological tests performed on the compound ALC-129 highlighted inhibitory activity on Caspase-3, selectivity with respect to Caspase-1, and potential neuroprotective activity for glutamate-induced toxicity (oxytosis). Labelled compound ¹¹C-ALC-129 has been prepared for Positron Emission Tomography (PET) preliminary studies.

Pyrazolines have played a crucial role in the development of various biologically active compounds. At the same time, the ferrocene moiety represents a significant part of the structure of these types of molecules. For this reason, we presumed that the incorporation of different pharmacophores in the same structure could lead to interesting changes, and we decided to synthesize some new ferrocenyl N-acyl pyrazolines. The DNA protective effect of four selected ferrocenyl N-acyl pyrazolines namely 5-methyl-3-ferrocenyl-4,5-dihydro-1H-pyrazole-1-carbaldehyde (3b), 1-(5,5-dimethyl-3-ferrocenyl-4,5-dihydro-1H-pyrazol-1-yl)ethanone (4c), 1-(5-(furan-2-yl)-3-ferrocenyl-4,5-dihydro-1H-pyrazol-1-yl)ethanone (4h), and 1-(3-ferrocenyl-4,5-dihydro-1Н-pyrazol-1-yl)propan-1-one (5a) in concentration of 100 μg/mL against hydroxyl and peroxyl radicals-induced DNA damage was assessed using salmon sperm DNA sodium salt as a model system. The acridine orange assay was performed to analyze the DNA integrity of the selected compounds at the same concentrations. The tested compounds in the selected dose had a statistically significant potency to protect DNA from damage caused by hydroxyl and peroxyl radicals. According to the acridine orange assay selected compounds significantly reduced hydroxy and peroxyl radicals induced denaturation and damage to DNA. The results showed that the tested compounds showed strong protective activity against hydroxy and peroxyl radicals-induced DNA damage.

Ocular myasthenia gravis (OMG) is an autoimmune disease in which Ab is produced against proteins at the neuromuscular junction in the ocular district, causing inability to contract extraocular and eyelid muscles and thus leading to muscle weakness, diplopia, ptosis, and therefore difficulty in vision. In cases where treatment with Acetylcholinesterase inhibitors fails, oral corticosteroids are used. One way to avoid the side effects of systemic administration of these drugs is their local administration. However, by topical administration, the percentage of drug absorbed in the eye is less than 5%. The use of oil-in-water nanoemulsions (NEs) to deliver corticosteroids increases their bioavailability and improves their absorption. The use of DABCO as a cationic surfactant for the formulation of the NEs allows a controlled drug release over time, through electrostatic interaction with the negatively charged mucins in the tears. DABCO's antibacterial properties also allow it to act as a preservative, making it possible to avoid the use of preservatives in the formulation, which are often responsible for allergic reactions. In this work, DABCO S2-NEs were produced and characterised, leading to the definition of a delivery system akin to ocular delivery, supporting the hypothesis of their use in the treatment of OMG. It is also possible to consider functionalising NEs with monoclonal antibodies (one of the latest treatments in the cure of the disease) to achieve a synergistic effect.

Both the metalloenzyme, New Delhi Metallo-β-lactamase-1 (NDM-1), and its reported variants, show multi-resistance to different antibiotics for the treatment of infectious diseases, due to their ability to hydrolyze a large number of beta-lactam compounds such a carbapenems, a factor that has an impact on microbial resistance, which is a worldwide concern. The present work shows initially, an in-silico study of some ADMET properties of potential NDM-1 enzyme inhibitors. A total of 56 compounds reported in the literature and the reference drugs meropenem and imipinem were used. Taking into account some values obtained with the online platform ADMETlab 2.0, of absorption, distribution, metabolism, excretion and toxicity, a filtering was performed, from which 22 compounds were generated, finding that the molecules with the best oral bioavailability and toxicity profile were derivatives of: ethylenediamine, N,N',N''-triacetate-1,4,7-triazacyclonononane, phosphonic acid ester mercaptans, sulfur-containing carboxylic acids, dipicolinic acid, cyclic borate, chromones, natural compounds and derivatives of thioamides. For this group of selected molecules, molecular docking was performed with AutoDock4 and AutoDock4Zn, the latter employing a specific force field for the docking of small molecules with zinc-containing metalloproteins, in order to compare whether there are point differences in the force fields applied in the different dockings. Finally, molecular dynamics calculations were performed for the best Dockings with GROMACS software, finding the best approximations of the possible real behavior of the analyzed molecular systems.

Brain tumors (BTs) represent a varied group of intracranial neoplasms. Among the treatment methods, radiotherapy is common. However, both the tumor and radiotherapy may induce oxidative stress, potentially impacting tumor progression and eliciting inflammation. This preliminary study aimed to assess the levels of C-reactive protein (CRP), melatonin, malondialdehyde (MDA), and protein carbonyl groups (PCO) in BT patients, both immediately before radiotherapy and 6-8 months after treatment. The study encompassed 16 patients (9 males and 7 females; average age of 51.75 ± 3.07 years) diagnosed with primary BT. Blood samples were procured at two timepoints: initially during the radiotherapy planning phase and, subsequently, after an average of 219.11 ± 14.40 days from the first collection. Blood serum samples underwent biochemical testing. A p-value of less than 0.05 was considered statistically significant. Results, expressed as mean value ± standard error of the mean (SEM), demonstrated a decrease in CRP levels from 11.01 ± 1.02 mg/L to 5.40 ± 0.54 mg/L. Melatonin levels remained comparable at 38.81 ± 2.40 pg/mL and 40.31 ± 2.29 pg/mL, respectively. MDA concentrations reduced from 483.86 ± 8.61 ng/mL to 454.25 ± 9.42 ng/mL, and PCO levels decreased from 200.33 ± 22.76 U/mL to 145.75 ± 6.20 U/mL. Statistically significant variations were noted in the levels of CRP, MDA, and PCO pre- and post-radiotherapy. Among long-term effects of BTs radiotherapy, a decrease of oxidative stress and inflammatory markers could be noticed. Those changes might be important for the patient's health improvement.

The impending growth of antimicrobial resistance has pushed research to explore alternative antibacterial strategies, including the use of metal-chelating agents since they can reduce the availability of essential metals for biological reactions and inhibit the biological function of metal-dependent proteins. Curiously, chelating medications also boost the efficiency of conventional antibacterials as well. In recent years, the focus has shifted to nanomaterials to improve the efficacy of medication delivery because they offer greater potential for penetration and retention in tissue. An interesting example is the halloysite, natural clay nanotubes consisting of close layers of alumina and silica, that has shown several advantages: the production process is not dangerous, it is less costly than other nanotubes, and it has advantageous features for drug delivery carrier applications. In this communication, we report the modification of halloysite nanotubes (HNTs) to produce a dual-acting material for drug delivery and iron chelation properties with antimicrobial activity. The structure of HNTs was modified with a derivative of Kojic acid. HNTs-kojic acid was characterized by several techniques: IR, ICP/MS, SEM, and EDX, and the drug delivery capabilities were proven by drug‐loading UV experiments with resveratrol and curcumin. Studies evaluating drug load capacity and encapsulation efficiency have shown that curcumin was characterized by slower kinetics compared to resveratrol, attributable to the different solubility of the two drugs. Moreover, the results of the antibacterial evaluation conducted on this new formulation because it has been proven that it exhibited antibacterial activity against both Gram-positive and Gram-negative bacteria at low concentrations. This suggests that the iron chelation action of the nanotubes is exceptionally efficient. These results open the way for additional investigation and the use of the designed material in treating cancer and other diseases with infections.

Current technological advances are resulting in an increased interest in computational methods for predicting the physicochemical properties of biological active compounds, such as lipophilicity, for example. There is a strong need to develop new and accurate in silico models that can be based on structural descriptors such as topological indices, which are sets of numerical descriptors that describe the molecule under study. The arrangement of atoms in a molecule is closely related to its topology and geometry, which correlates with the pharmacokinetic properties of the substance, such as ADME/T. In this study, Wiener (W), Randić (⁰χ, ¹χ, ⁰χ^ν, ¹χ^ν), Gutman (M, M^ν), Pyka (A, ⁰B, ¹B) and Rouvray-Crafford (R) topological indices were calculated for selected antimicrobial compounds such as delafloxacin, linezolid, sutezolid, ceftazidime and selected immunosuppressive compounds like everolimus and zotarolimus. Linear regression analysis was used to create linear correlations between the calculated topological indices and the values of lipophilicity parameters previously obtained by TLC technique and calculated by computer algorithms. Our work indicates that structural descriptors like topological indices can be a useful tool for predicting selected important ADME/T properties of drugs, such as lipophilicity. The best predictive power (r>0.9) indicate the linear models based on the following topological indices: R,W,A. The proposed method is fast, easy to use, and economical because it avoids expensive laboratory experiments to study ADME/T properties by experimental methods.

Yeast are an important group of single-celled microorganisms employed in the traditional fermentation, biotechnology and life science. However, some yeasts act as pathogens in humans, causing serious infections and even death. The other yeasts can cause spoilage of food and significant economic loss. Various preservatives are utilized to suppress yeast growth in food, and several antifungal medications are used to treat yeast infections. However, the increasing resistance of yeasts to commonly used organic compounds in both medicine and food industry, as well as the demand from users for safer and more effective substances, pose a challenge in the search for new drugs and preservatives. Quinazolinones and their transition-metal complexes represent versatile compounds with broad spectrum of biological activities. Thus, the aim of this study was the evaluation of biological properties of quinazolinone ligands and their copper complexes. Compounds were screened for antifungal potential against a panel of both pathogenic yeast species and the yeast species which cause food spoilage. The species examined included Candida albicans, C. glabrata, C. parapsilosis, C. tropicalis, Pichia kudriavzevii of the human origin, and a panel of yeasts which cause food spoilage, such as P. membranifaciens, Zygosaccharomyces bailii, Z. rouxii, and Yarrowwia lipolytica. Results showed that the Cu(II) complexes were much more effective than free ligands, and the most potent complex displayed strong inhibition activity towards 80% of all the tested strains. This study revealed that coordination with Cu(II) ion play an important role in enhancing the biological activity.

Adipose tissue performs important endocrine functions. In the case of obesity, which is associated with chronic inflammation, the balance in the release of adipokines is disturbed. Metabolic disorders of adipose tissue may contribute to the development and progression of cancer, including neuroendocrine neoplasms (NENs). The aim of this study was to determine the concentration of leptin, omentin-1, visfatin and resistin in healthy people and in patients with NENs of the gastrointestinal tract, pancreas and lung. The study included 68 patients of the Prof. F. Łukaszczyk Oncology Center in Bydgoszcz with NENs of the gastrointestinal tract (GT, n=34), NENs of pancreas (PA, n=22), NENs of lungs (L, n=12) and in the control group (CTRL, n=35). The concentration of the adipokines was measured by the enzyme immunoassay method using ready-made ELISA kits and Bio-Plex Pro Human Diabetes. A statistical analysis was performed and P<0.05 was considered as statistically significant. The results were presented as the mean value and the standard error of the mean. There were statistically significant changes in the levels of visfatin and resistin in patients with NENs compared to CTRL, but no statistically significant difference was found in the concentration of leptin, an adipokine responsible for regulating the body's energy storage. The concentrations of the measured adipokines were similar in the analyzed subgroups of NENs. However, a statistically significant increase in omentin-1 concentration was observed in patients with NENs, the only tested adipokine with anti-inflammatory activity, which may have a prognostic significance.