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The mechanisms of antigen processing and presentation play a crucial role in the recognition and targeting of cancer cells by the immune system. Cancer cells can evade the immune system by downregulating or losing the expression of the proteins recognized by the immune cells as antigens, creating an immunosuppressive microenvironment, and altering their ability to process and present antigens. This review focuses on the mechanisms of cancer immune evasion with a specific emphasis on the role of antigen presentation machinery. The study of the immunopeptidome, or peptidomics, has provided insights into the mechanisms of cancer immune evasion and has potential applications in cancer diagnosis and treatment. Additionally, manipulating the epigenetic landscape of cancer cells plays a critical role in suppressing the immune response against cancer. Targeting these mechanisms through the use of HDACis, DNMTis, and combination therapies has the potential to improve the efficacy of cancer immunotherapy. However, further research is needed to fully understand the mechanisms of action and optimal use of these therapies in the clinical setting.

Lung cancer is considered to account for approximately one-fifth of all malignant tumor-related deaths worldwide and is therefore one of the most lethal malignancies. Pyrazole scaffold possesses a wide range of biological and pharmacological activities, which play important roles in medicinal chemistry. The present study reports the synthesis and in vitro biological characterization of nine pyrazoles derived from chalcones as potential anticancer agents for non-small cell lung cancer A-549, H226, and H460 cell lines. Most of the compounds efficiently inhibited the growth of all the tested cancer cell lines at micromolar concentrations. One of the most active compounds ( PCH-1 ) was further evaluated for its effect on cell cycle distribution, apoptosis, migration, epithelial–mesenchymal transition, and oxidative stress. Furthermore, studies on the mechanism of action revealed that PCH-1 disrupts microtubule assembly, leading to cancer cell death. Molecular modeling studies confirmed the potent interaction of PCH-1 with the vinblastine binding site on tubulin. Overall, this study provides novel opportunities to identify anticancer agents in the pyrazole series.

Anthraquinones have attracted considerable interest in the realm of cancer treatment owing to their potent anticancer properties. This study evaluates the potential of a series of new anthraquinone derivatives as anticancer agents for non-small-cell lung cancer (NSCLC). The compounds were subjected to a range of tests to assess their cytotoxic and apoptotic properties, ability to inhibit colony formation, pro-DNA damage functions, and capacity to inhibit the activity of tyrosine kinase proteins (PTKs). Based on the research findings, it has been discovered that most active derivatives ( , , and ) possess a substantial capability to impede the viability of NSCLC while having mostly a negligible effect on the human kidney cell line. Moreover, the anthraquinones displayed pro-apoptotic and genotoxic attributes while blocking the phosphorylation of multiple PTKs. Collectively, our findings indicate that these derivatives may demonstrate promising potential as effective anticancer agents for lung cancer treatment.

Colorectal cancer (CRC) is the most commonly diagnosed cancer in Europe and the United States and the second leading cause of cancer related mortality. A therapeutic strategy used for the treatment of CRC involves targeting the intracellular levels of reactive oxygen species (ROS). In this study, we synthesized a series of novel tetrahydroquinolinones and assessed their ability to inhibit CRC growth and proliferation by evoking cellular stress through ROS. Our results revealed that (2-oxo-4-phenyl-5,6,7,8-tetrahydroquinolin-8-yl) N-(3-fluorophenyl)carbamate ( 20d ) exhibited in vitro antiproliferative activity at micromolar concentrations. The compound also suppressed colony formation and the migration of HCT-116 cells, as well as deregulated the expression of several proteins involved in cell proliferation and metastasis. Furthermore, 20d induced massive oxidative stress by disrupting the balance of cells survival resulting in autophagy via the PI3K/AKT/mTOR signaling pathway. These findings suggest that this tetrahydroquinolinone can be an ideal lead compound for drug discovery based on quinone derivatives.

The anticancer properties of quinolones is a topic of interest among researchers in the scientific world. Because these compounds do not cause side effects, unlike the commonly used cytostatics, they are considered a promising source of new anticancer drugs. In this work, we designed a brief synthetic pathway and obtained a series of novel 8-phenyltetrahydroquinolinone derivatives functionalized with benzyl-type moieties at position 3. The compounds were synthesized via classical reactions such as nucleophilic substitution, solvent lysis, and condensation. Biological evaluation revealed that 3-(1-naphthylmethyl)-4-phenyl-5,6,7,8-tetrahydro-1H-quinolin-2-one ( 4a ) exhibited potent cytotoxicity toward colon (HTC-116) and lung (A549) cancer cell lines. Analysis of the mechanism of action of compounds showed that compound 4a induced cell cycle arrest at the G 2 /M phase, leading to apoptotic cell death via intrinsic and extrinsic pathways. Taken together, the findings of the study suggest that tetrahydroquinolinone derivatives bearing a carbonyl group at position 2 could be potential lead compounds to develop anticancer agents for the treatment of lung cancers.

The sea trout Salmo trutta has considerable ecological and economic importance in the Baltic Sea basin. In recent years, the landings of this species from the Main Basin have decreased significantly. Consequently, it is necessary to consider whether this decline has been associated with any changes in the diversity and domination of its parasitofauna. We examined 101 sea trout specimens originating from the southern Baltic Sea basin and its tributary (the Gulf of Gdańsk and the River Reda) collected between 2003 and 2020. The fish were infected with five parasite species: one tapeworm (Eubothrium crassum), one digenean (Brachyphallus crenatus), and three nematodes (Anisakis simplex, Hysterothylacium aduncum, and Raphidascaris acus). Overall parasite prevalence was high (parasites were found in 94.7% of sea trout), with a mean intensity of 37.4 and a range of 1–125 parasites per fish. Eubothrium crassum, a species widely distributed in Europe and North America, clearly dominated the parasite community: a total of 3345 specimens were recorded in 92.6% of fish, with a mean intensity of 38.0 and an intensity range of 1–125 individuals. Correct morpho-anatomical identification was confirmed by molecular methods. The tapeworms were located primarily (96%) in the pyloric caeca. Other parasite species occurred only sporadically. Infection levels increased with both the length and mass of the fish; however, despite the high parasite infection, no deterioration in the host was indicated by Fulton’s condition factor. Comparison of fish originating from the different time periods revealed no changes in their parasitological characteristics, suggesting that parasite–host interactions are unlikely to have contributed to the decline in fish catches.

With the current massive increases in drug-resistant microbial infection as well as the significant role of fungal infections in the death toll of COVID-19, discovering new antifungals is extremely important. Natural and synthetic xanthones are promising derivatives, although only few reports have demonstrated their antifungal mechanism of action in detail. Newly synthetized by us xanthone derivative 44 exhibited strong antifungal activity against reference and fluconazole resistant C. albicans strains. Our results indicate that the most active compounds 42 and 44 are not substrates for fungal ABC transporters (Cdr1p and Cdr2p) and Mdr1p, the main representative of the major facilitator superfamily efflux pumps, membrane proteins that are responsible for the development of resistance. Moreover, fungicidal mode of action reduces the probability of persistent or recurrent infections and resistance development. In this light, the demonstrated killing activity of the examined derivatives is their undoubted advantage. Novel synthesized compounds exhibited moderate cytotoxicity against human cell lines, although the selectivity index value for human pathogenic strains remained favourable. Our results also indicate that novel synthetized compounds 42 and 44 with antifungal activity target yeast topoisomerase II activity. In summary, further validation of xanthones applicability as antifungals is highly valuable.

The development of selective anticancer agents remains a central objective in medicinal chemistry. Here, we report the synthesis, structural characterization, and biological evaluation of the first metal complex of a quinoline-based thiazolyl-hydrazone ligand [( E )-2-(8-(quinolin-2-ylmethylene)hydrazinyl)-4-(4-tolyl)-1,3-thiazole)] ( HL ). Obtained octahedral Zn(II) complex [Zn(HL) 2 ](NO 3 ) 2 , ( 1 ), is based on two NNN tridentate coordinated ligands. In vitro cytotoxicity assays revealed that the complex exhibits potent and selective activity against lung adenocarcinoma A-549 and colorectal carcinoma HCT-116, while sparing non-tumorigenic human embryonic kidney HEK-293 cells. Mechanistic studies demonstrated that the complex induces S-phase arrest, inhibits DNA synthesis, and triggers significant DNA damage as indicated by increased p-γH2AX expression. These effects were accompanied by mitochondrial depolarization, caspase-3/7 activation, and phosphatidylserine externalization, confirming apoptosis via the intrinsic pathway. The compound further inhibited tumor growth in 3D spheroids and the chick chorioallantoic membrane model without overt toxicity. Compared to the free ligand and reference chemotherapeutics, the zinc complex showed improved efficacy and selectivity. These results highlight the potential of metal coordination to enhance the biological activity of hybrid ligands, supporting further development of this class of compounds as selective anticancer agents.

Fungal pathogens are considered as serious factors for deadly diseases and are a case of medical concern. Invasive fungal infections also complicate the clinical course of COVID-19, leading to a significant increase in mortality. Furthermore, fungal strains' multidrug resistance has increased the demand for antifungals with a different mechanism of action. The present study aimed to identify antifungal compounds targeting yeast topoisomerase II (yTOPOII) derived from well-known human topoisomerase II (hTOPOII) poisons C-1305 and C-1311 . Two sets of derivatives: triazoloacridinones ( IKE1-8 ) and imidazoacridinones ( IKE9-14 ) were synthetized and evaluated with a specific emphasis on the molecular mechanism of action. Our results indicated that their effectiveness as enzyme inhibitors was not solely due to intercalation ability but also as a result of influence on catalytic activity by the formation of covalent complexes between plasmid DNA and yTOPOII. Lysine conjunction increased the strength of the compound's interaction with DNA and improved penetration into the fungal cells. Triazoloacridinone derivatives in contrast to starting compound C-1305 exhibited moderate antifungal activity and at least twice lower cytotoxicity. Importantly, compounds ( IKE5-8 ) were not substrates for multidrug ABC transporters whereas a derivative conjugated with lysine ( IKE7 ), showed the ability to overcome C. glabrata fluconazole-resistance (MIC 32–64 µg mL −1 ).