Progressive supranuclear palsy (PSP) is an atypical parkinsonian syndrome based on tau pathology; its clinical phenotype differs, but PSP with Richardson’s syndrome (PSP-RS) and the PSP parkinsonism predominant (PSP-P) variant remain the two most common manifestations. Neuroinflammation is involved in the course of the disease and may cause neurodegeneration. However, an up-to-date cytokine profile has not been assessed in different PSP phenotypes. This study aimed to evaluate possible differences in neuroinflammatory patterns between the two most common PSP phenotypes. Serum and cerebrospinal fluid (CSF) concentrations of interleukin-1 beta (IL-1β) and IL-6 were analyzed using enzyme-linked immunosorbent assay (ELISA) kits in 36 study participants—12 healthy controls and 24 patients with a clinical diagnosis of PSP-12 PSP-RS and 12 PSP-P. Disease duration among PSP patients ranged from three to six years. All participants underwent basic biochemical testing, and neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) values were calculated. Due to a lack of neuropathological examinations, as all patients remain alive, total tau levels were assessed in the CSF. Tau levels were significantly higher in the PSP-P and PSP-RS groups compared to the healthy controls. The lowest concentrations of serum and CSF interleukins were observed in PSP-RS patients, whereas PSP-P patients and healthy controls had significantly higher interleukin concentrations. Furthermore, there was a significant correlation between serum IL-6 levels and PLR in PSP-RS patients. The results indicate the existence of distinct neuroinflammatory patterns or a neuroprotective role of increased inflammatory activity, which could cause the differences between PSPS phenotypes and clinical course. The causality of the correlations described requires further studies to be confirmed.

Phenothiazine derivatives are widely studied in various fields such as biology, chemistry, and medicine research because of their pharmaceutical effects. The first compound used successfully in the treatment of psychosis was a phenthiazine derivative, chlorpromazine. Apart from its activity in neurons, chlorpromazine has also been reported to display anticancer and antibacterial properties. In this study, we present the synthesis and research on the activity of A549, MDA, MiaPaCa, PC3, and HCT116 cancer cell lines and of S. aureus, S. epidermidis, E. coli, and P. aeruginosa bacterial strains against a series of new tetracyclic chlorpromazine analogues containing a quinoline scaffold in their structure instead of the benzene ring and various substituents at the thiazine nitrogen. The structure of these novel molecules has been determined by ¹H NMR, ¹³C NMR, and HRMS spectral techniques. The seven most active of the twenty-four new chlorpromazine analogues tested were selected to study the mechanism of cytotoxic action. Their ability to induce apoptosis or necrosis in cancer cells was assessed by flow cytometry analysis. The results obtained confirmed the proapoptotic activity of selected compounds, especially in terms of inducing late apoptosis or necrosis in cancer cell lines A549, MiaPaCa-2, and HCT-116. Furthermore, studies on the induction of cell cycle arrest suggest that the new chlorpromazine analogues exert antiproliferative effects by inducing cell cycle arrest in the S phase and, consequently, apoptosis.

Progressive supranuclear palsy (PSP) is a tauopathic atypical parkinsonian syndrome. Recent studies suggest that inflammation may play a role in PSP pathogenesis, highlighting markers like the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and cytokines such as IL-1β and IL-6. This study aimed to assess the relationship between peripheral inflammatory markers and psychological abnormalities in PSP-RS and PSP-P patients. The study included 24 participants: 12 with PSP-RS, 12 with PSP-P, and 12 controls. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA); however, the executive functions were evaluated using the Frontal Assessment Battery (FAB), while inflammatory markers such as IL-1β, IL6, NLR, and PLR were measured. The parameter correlation was executed using Spearman’s correlation (rs). The analysis revealed significant negative correlations between NLR and MoCA (rs = −0.48), as well as between PLR and MoCA (rs = −0.60). The negative correlation between IL-1β and MoCA was statistically significant but relatively weak. This study highlights the relevance of inflammatory markers such as NLR and PLR in reflecting cognitive decline in PSP patients, with IL-1β potentially playing a protective role in cognitive function.

Progressive supranuclear palsy (PSP) is a condition classified as atypical parkinsonism. Pathologically, it is a four-repeat tauopathy; clinically, it is a disease comprising oculomotor dysfunction, postural instability, akinesia, and cognitive/language disorders. Its pathogenesis is not fully recognized; however, neuroinflammation is considered to likely be a significant aspect, though it is not known whether inflammation is a cause or consequence of neurodegeneration. In this study, the authors analyzed the association between inflammatory/neurotrophic factors and parameters linked to quality of life, based on examinations of 10 controls and 11 patients with PSP. They found a negative correlation between mPSPRS (Modified Progressive Supranuclear Palsy Rating Scale) and the glial cell-line-derived neurotrophic factor levels (GDNF) (r = −0.772727, p = 0.003) in the serum, a less pronounced negative correlation between progressive supranuclear palsy–quality of life parameter (PSP-QoL) and GDNF (r = −0.68390, p = 0.011) in the serum, and no correlations were observed in the analyses of inflammatory factors. The obtained results show the association between lower levels of GDNF and more pronounced clinical deterioration. Further analysis in the field based on larger groups of patients is required.

The presented results are a continuation of our research on the synthesis and biological properties of halogen benzofuran derivatives, particularly their anticancer potential. We examined the cytotoxicity of two derivatives, methyl 4-chloro-6-(dichloroacetyl)-5-hydroxy-2-methyl-1-benzofuran-3-carboxylate (7) and methyl 6-(dibromoacetyl)-5-methoxy-2-methyl-1-benzofuran-3-carboxylate (8), in the following human cancer cell lines: SW480, SW620, HCT116, HepG2, PC3, A549, and MDA. The MTT assay results showed that compound 7 exhibited the most promising activity against A549 cells, while compound 8 demonstrated significant activity against both A549 cells and HepG2 cells. The biological activity of these compounds was evaluated by the trypan blue assay, reactive oxygen species generation, lipid peroxidation and IL-6 secretion. To investigate the proapoptotic activity of these compounds, the two following types of tests were performed: Annexin V Apoptosis Detection Kit I and Caspase-Glo 3/7 assay. Moreover, we checked the effect of both tested derivatives on the cell cycle and tubulin polymerization. The obtained results revealed that the presence of bromine and methoxy group in the structure has an influence on the biological properties of compound 8. This derivative exhibited stronger pro-oxidative effects and proapoptotic properties compared to those observed for derivative 7. Both compounds decreased IL 6 secretion in the tested cancer cell lines; however, the stronger effect was observed for HepG2 cells. Analysis of the cell cycle in the presence of the tested compounds revealed that compound 7 induced G2/M phase arrest in HepG2 cells, while compound 8 caused cell cycle arrest at the S and G2/M phases in A549 cells. On the other hand, both derivatives had a minimal effect on tubulin polymerization. These findings suggest that compounds 7 and 8 could serve as starting points for further development of anticancer agents.

Phenothiazine derivatives are widely studied in various fields such as biology, chemistry, and medicine research because of their pharmaceutical effects. The first reagent that was used suc-cessfully in the treatment of psychosis was a phenthiazine derivative, chlorpromazine. Apart from their activity in neurons, chlorpromazine have also been reported to display anticancer and antibacterial properties. In these studies, we present the synthesis and research on the activ-ity against A549, MDA, MiaPaCa, PC3 and HCT116 cancer cell lines and against S. aureus, S. epi-dermidis, E. coli and P. aeruginosa bacterial strains a series of new tetracyclic chlorpromazine ana-logues containing a quinoline scafford in their structure instead of the benzene ring and various substituents at the thiazine nitrogen. The structure of these novel molecules has been deter-mined by 1H NMR, 13C NMR and HRMS spectral techniques. The seven most active of the twen-ty-four new chlorpromazine analogues tested were selected for study of the mechanism of cyto-toxic action. Their ability to induce apoptosis or necrosis in cancer cells was assessed by flow cytometry analysis. The results obtained confirmed the proapoptotic activity of selected com-pounds, especially in terms of inducing late apoptosis or necrosis in cancer cell lines A549, Mi-aPaCa-2 and HCT-116. Furthermore, studies on the induction of cell cycle arrest suggest that the new chlorpromazine analogues exert antiproliferative effects by inducing cell cycle arrest in the S phase and, consequently, apoptosis.