Pyrimidine derivatives exhibit a wide range of biological activities, including anti-inflammatory properties. The aim of this study was to investigate the effects of tested pyrimidine derivatives on the activity of cyclooxygenase isoenzymes (COX-1 and COX-2), antioxidant properties, and their ability to inhibit the growth of inflammatory cells. In vitro tests were conducted to assess the ability of pyrimidine derivatives L1–L4 to inhibit COX-1 and COX-2 activity using the TMPD oxidation assay (N,N,N′,N′-tetramethyl-p-phenylenediamine). The compounds’ ability to inhibit the growth of lipopolysaccharide (LPS)-stimulated THP-1 (human leukemia monocytic) monocyte cells and their impact on reactive oxygen species (ROS) levels in an inflammatory model were also evaluated. The binding properties of human serum albumin (HSA) were assessed using UV–Vis spectroscopy, circular dichroism (CD), and isothermal titration calorimetry (ITC). Among the tested pyrimidine derivatives, L1 and L2 showed high selectivity towards COX-2, outperforming piroxicam and achieving results comparable to meloxicam. In the sulforhodamine B (SRB) assay, L1 and L2 demonstrated dose-dependent inhibition of LPS-stimulated THP-1 cell growth. Additionally, ROS assays indicated that these compounds reduced free radical levels, confirming their antioxidant properties. Binding studies with albumin revealed that L1 and L2 formed stable complexes with HSA. These results suggest that these compounds could serve as a basis for further research into anti-inflammatory and anticancer drugs with reduced toxicity.

A series of novel N-Mannich bases derived from a dimethylpyridine–1,2,4-triazole hybrid was synthesized and evaluated in vitro for cytotoxic activity on several human gastrointestinal cancer cells (EPG, Caco-2, LoVo, LoVo/Dx, and HT-29). Compound 6 bearing a phenyl group at the N-4 position and a 4-methylphenyl piperazine moiety at the N-2 position of the 1,2,4-triazole-3-thione scaffold exerted good cytotoxic activities on EPG and Caco-2 cell lines, along with pronounced selectivity, showing lower cytotoxicity against normal colonic epithelial cells (CCD 841 CoTr). Further evaluation revealed the good ability of compound 6 to inhibit the efflux function of P-glycoprotein in P-gp-expressing cell lines (HT-29, LoVo, and LoVo/Dx). Moreover, compound 6 induced apoptotic cell death through a significant increase in the caspase-3 and p53 protein levels in HT-29 cells. Finally, the molecular docking method was applied to explain our experimental findings. The molecular modeling study based on Density Functional Theory (DFT) and the Quantum Theory of Atoms in Molecules (QTAIM) analysis provided insight into the geometric and electronic structure properties of the compounds.

The design of novel anti-inflammatory drugs remains a critical area of research in the development of effective treatments for inflammatory diseases. In this study, a series of 1,2-benzothiazine was evaluated through a multifaceted approach. In particular, we investigated the potential interactions of the potential drugs with lipid bilayers, an important consideration for membrane permeability and overall pharmacokinetics. In addition, we evaluated their ability to inhibit cyclooxygenase 1 and cyclooxygenase 2 activity and selectivity using both a cyclooxygenase inhibition assay and molecular docking simulations. To evaluate their therapeutic potential, we performed in vitro assays to measure cytokine mRNA expression in inflamed cells. The antioxidant activity was evaluated using both in vitro assays, such as 2,2-diphenyl-1-picrylhydrazyl and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid scavenging, to determine the compounds’ capacity to neutralize free radicals and reduce oxidative stress. Theoretical calculations, including density functional theory, were used to predict the reactivity profiles of the compounds.

Background: The COVID-19 pandemic necessitated rapid and widespread vaccination efforts, which proved critical in reducing the severity and mortality of the virus. However, the interplay between vaccinations, pre-existing skin conditions, and other comorbidities still needs to be explored. This study investigated the occurrence and severity of adverse events following immunization (AEFIs) with COVID-19 vaccines in individuals with chronic skin diseases and comorbidities within a Central European cohort. Methods: An anonymous online survey was conducted between May 2022 and February 2023, targeting students and employees of universities in Wrocław, Poland. A total of 513 respondents were analyzed, focusing on AEFIs following the first, second, and third doses of COVID-19 vaccines and the effects of COVID-19 on conditions such as atopic dermatitis, psoriasis, vitiligo, acne vulgaris, rosacea, and various comorbidities. Results: COVID-19 vaccination effectively protected against severe disease across all doses. The analysis revealed no significant impact of either COVID-19 infection or vaccination on the course of selected skin diseases and comorbidities. The reporting of AEFIs to the Sanitary Inspection was notably low. The Moderna and Pfizer mRNA-based vaccines were associated with a higher reported number of AEFIs, particularly after the second and third doses, compared to AstraZeneca, which exhibited fewer adverse events after subsequent doses. Conclusions: COVID-19 vaccination is both safe and effective, even in patients with pre-existing skin conditions and comorbidities. Vaccine selection may benefit from considering individual health profiles, and better reporting of AEFIs is needed to enhance vaccine safety monitoring.

Background/Objectives: This study investigated the anticancer potential of an aqueous extract of the fungus Fomitopsis betulina. Methods: The study assessed the effect of the extract on nine cancer cell lines, including melanoma (LM-MEL-75), lung cancer (A549), and colorectal cancer (HT29, LoVo), and four normal cell lines. The cytotoxicity of the extract was evaluated using MTT, sulforhodamine-B (SRB), and clonogenic viability assays. Additionally, the study examined the effect of the extract on plant model organisms, garden cress (Lepidium sativum) and common onion (Allium cepa), to further investigate its biological activity. Results: The assays demonstrated selective cytotoxicity of the extract toward cancer cells, while sparing normal cells. The extract induced significant cytotoxic effects at lower concentrations in lung cancer, melanoma, and colon cancer cells, showing promise as a potential anticancer agent. The results also revealed that the extract inhibited seed germination and root growth, suggesting its potential to disrupt cell cycles and induce apoptosis. Conclusions: This study highlights the therapeutic potential of F. betulina and highlights the need for further research to identify the active ingredients and mechanisms underlying its anticancer effects.