In this study, a series of novel 2-alkyl(aryl)-quinazolin-4(3H)-thiones, 2-R-(quinazolin-4(3H)-ylthio)carboxylic acids and amides were synthesized and evaluated for antimicrobial and anticancer activities. Their structure was confirmed by elemental analysis and spectral data (FT-IR, LC-MS, (1)H-NMR). Antimicrobial activity was tested in vitro against Staphylococcus aureus, Enterococcus faecalis, Enterobacter aerogenes, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumonia, Candida albicans and NCI in vitro preliminary anticancer activity against nine different cancer types. The most active antibacterial and antifungal compounds were: 2.1, 2.2 and 2.4. The introduction of the carboxylic acid or amide residue into the fourth position of quinazolin-4(3H)-thione resulted in the absence of antimicrobial activity. Substance 3.8 inhibited renal cancer UO-31 line and 2.18 - leukemia CCRF-CEM. The results of in silico molecular docking for DHFR and CK2 kinase had no correlation with in vitro properties, proposing the presence of other biological activity pathways.

The peculiarities of the reaction between 3-(2-aminophenyl)-6-R-1,2,4-triazin-5(2H)-ones and cyclic anhydrides of non-symmetric (2-methylsuccinic, 2-phenylsuccinic and camphoric) acids have been described in the present article. The influence of electronic and steric effects of substituents in the anhydride molecule on cyclisation processes has been discussed. The results have shown that the interaction of 3-(2-aminophenyl)-6-R-1,2,4-triazin- 5(2H)-ones mentioned above with 2-methylsuccinic and 2-phenylsuccinic acid anhydrides proceeded non-selectively and yielded the mixtures of 2-R1-3-(2-oxo-3-R-2H-[1,2,4]triazino[2,3-c]quinazoline-6-yl)propanoic acids and 1-(2-(5-oxo-6-R-2,5-dihydro-1,2,4-triazin-3-yl)phenyl)-3-R1-pyrrolidine-2,5-diones. It has been found that low regioselectivity of the acylation process may be explained by insignificant electronic effects of substituents (of the methyl and phenyl fragment) in position 2 of the anhydride molecule on the electrophilic reaction centre. It has been also determined that the reaction between 3-(2-aminophenyl)-6-R-1,2,4-triazin-5(2H)-ones and camphoric anhydride proceeds regioselectively and yielded 1,2,2-trimethyl-3-(3-R-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazolin- 6-yl)cyclopentan-1-carboxylic acids. Regioselectivity of the interaction mentioned above may be explained by the steric effect of the methyl group. Identity of compounds has been proven by LC-MS, the structure has been determined via a set of characteristic signals in 1H NMR, 13C NMR spectra and position of cross peaks in the correlation HSQC-experiment. Mass spectra of the compounds synthesized have been also studied, the principal directions of the molecule fragmentation have been described. The structure of 1,2,2-trimethyl-3-(3-methyl- 2-oxo-2H-[1,2,4]triazino[2,3-c]quinazolin-6-yl)cyclopentane-1-carboxylic acid has been proven by X-ray analysis.

Ferroptosis is a novel form of regulated cell death that plays a key role in the pathogenesis of a wide range of multifactorial diseases. Its uniqueness lies in the iron-dependent accumulation of lipid peroxides, which distinguishes it from apoptosis, necroptosis, and autophagy. Understanding the molecular mechanisms of ferroptosis opens up new therapeutic prospects, but the dual role of this process – both as a factor of malignant cell death and a mediator of tissue damage – creates significant challenges for clinical application. The paper systematizes current ideas about the molecular mechanisms of ferroptosis regulation, including iron metabolism, lipid peroxidation, and antioxidant defense systems. Signaling pathways that modulate sensitivity to ferroptosis are analyzed. Particular attention is paid to the dual role of ferroptosis in the pathogenesis of diseases: induction of ferroptosis is considered a promising strategy for overcoming the resistance of malignant neoplasms to chemotherapy, immunotherapy and radiotherapy, while its inhibition is critical for protecting tissues from ischemia-reperfusion injury, neurodegeneration and inflammation. Key counterarguments are highlighted, in particular the pro-inflammatory and immunosuppressive effects of ferroptosis, which may contribute to tumor progression. Ferroptosis is a universal mechanism of cell death with powerful therapeutic potential, however, its clinical implementation requires a differentiated approach depending on the pathological context. Promising directions are the development of highly selective modulators, identification of specific biomarkers of ferroptosis in vivo and conducting well-designed clinical trials. In-depth study of molecular regulatory networks will allow translating fundamental knowledge into personalized treatment strategies for multifactorial diseases.

This work provides a comprehensive analysis of the current state and future prospects of lipidomics. Lipidomics is a critical tool in systems biology and translational medicine. The study substantiates the concept that lipidomics possesses high transformative potential. This potential is necessary for deciphering the pathogenesis of complex diseases and discovering new biomarkers. The full practical realization of this potential is possible only by overcoming analytical barriers and systematically integrating with other omics technologies. The fundamental role of lipids in cellular processes is highlighted. The necessity of a systemic approach to their identification is demonstrated. The work is divided into three logical blocks. The first block examines the methodological foundations of mass spectrometry ("shotgun" lipidomics, LC-MS/MS, MALDI-MSI, IM-MS) and analyzes their limitations in detail. Particular attention is paid to the phenomenon of in-source fragmentation. This leads to the generation of spectral artifacts and erroneous lipid species annotation. Challenges related to the separation of structural and stereoisomers are also discussed. The second block reveals the clinical potential of lipidomics. Examples of cardiovascular, neurodegenerative, metabolic, and oncological pathologies are considered. The third block is devoted to multi-omics integration and the application of artificial intelligence methods. These are necessary for moving from observational correlations to causal mechanisms. Priority directions for future research are formulated. Protocol standardization and the implementation of high-resolution analytical methods for clinical practice are discussed.

Chronic non-communicable diseases (NCDs) constitute the leading cause of global morbidity and mortality. Over recent decades, chronic inflammation has been increasingly recognized not merely as an epiphenomenon of distinct clinical entities, but rather as an overarching pathogenetic mechanism uniting neurodegenerative, metabolic, oncological, autoimmune, allergic, and age-related disorders. This underscores the imperative for a comprehensive analysis across its molecular, cellular, and therapeutic facets. Consequently, this review aims to map and synthesize contemporary data concerning molecular pathways, cellular effectors, and therapeutic modalities for the modulation of chronic inflammation through a literature-based approach. A narrative review of the scientific literature – encompassing experimental, clinical, and review studies – was conducted to elucidate the role of inflammation in the pathogenesis of chronic diseases. The findings establish chronic inflammation as a universal pathogenetic mechanism underlying various chronic non-communicable diseases. Its molecular architecture encompasses the NF-κB, JAK-STAT, MAPK, PI3K/Akt/mTOR, HIF-1α, and AMPK/SIRT1/PPARγ signaling pathways, the NLRP3 inflammasome, and a complex cytokine network (TNF-α, IL-1β, IL-6, IL-17, IL-18, IL-33, TGF-β, and IL-10). Key cellular effectors span immune populations – including macrophages, neutrophils, dendritic cells, natural killer (NK) cells, T and B lymphocytes, and group 2 innate lymphoid cells (ILC2s) – as well as non-immune and parenchymal cell lineages, such as adipocytes, hepatocytes, myocytes, fibroblasts, and senescent cells, all demonstrating marked phenotypic plasticity. Therapeutic modalities – spanning anti-cytokine agents, NLRP3 inflammasome inhibitors, Janus kinase (JAK) inhibitors, metabolic modulators, antioxidants, natural phytochemicals, microbiome-directed therapies, senolytics, and targeted delivery platforms – exhibit substantial promise, yet demand a precision medicine framework owing to the context-dependent, pleiotropic nature of specific mediators and the inherent heterogeneity of inflammatory phenotypes. Chronic inflammation represents a pivotal pathogenetic driver underlying various chronic non-communicable diseases. Its molecular and cellular components form an integrated, highly dynamic network, offering a viable and high-value target for therapeutic intervention. High-priority research directions encompass multi-omics studies, the discovery and validation of robust inflammatory biomarkers, and the formulation of personalized and combinatorial therapeutic frameworks.