Background. Tuberculosis therapy can lead to considerably dissimilar outcomes among individual patients. Some patients benefit from anti-tuberculosis chemotherapy leading to a desired therapeutic effect, while other patients show insufficient or absent response, or develop adverse side effects. Individual response to isoniazid is affected by mutations in the gene encoding N-acetyltransferase 2 (NAT2). Wide variations were observed in distributions of polymorphic NAT2 alleles in human populations depending on race, ethnicity, or geographical origin. No data are available to date on prevalence of NAT2 gene polymorphic variants and acetylation types in Yakut (Sakha) patients with newly diagnosed pulmonary tuberculosis. Aims: the frequencies of NAT2 polymorphic SNPs as well isoniazid acetylation phenotypes were evaluated in the patients cohort of Yakut ethnicity with newly diagnosed pulmonary tuberculosis (PTB). The comparison with, other ethnic groups of Asian origin was done. Methods. Cross-sectional study was conducted among Yakut patient cohorts with newly identified pulmonary tuberculosis. Using real-time PCR the following SNPs were explored: NAT2*5 (rs1801280, Т341С), NAT2*6 (rs1799930, G590A), NAT2*7 (rs1799931, G857A), NAT2*11 (rs1799929, C481T), NAT2*12 (rs1208, A803G), NAT2*13 (rs1041983, C282T). Genetically determined metabolic rates were calculated using NATpred online tool. Results. NAT2 SNPs were assessed, namely *5, *6, *7, *11, *12, and *13. The most frequent in Yakut patients were NAT2*6 and NAT2*13 SNPs (40.9% and 64.4%, respectively). Significant differences were detected in frequencies of NAT2 *5, *11, *12 polymorphisms; all studied NAT2 gene polymorphisms showed meaningful differences in genotype and minor allele prevalence rates after comparison between Yakut population and other Mongoloid ethnic groups (populations of China, Japan, Vietnam). High prevalence of intermediate acetylation type among ethnic Yakuts (58.3%) was established. Conclusions. Certain distinct differences in allelic variants of NAT2 gene and acetylation type prevalence in patients of Yakut ethnic origin newly diagnosed with pulmonary tuberculosis let conclude that the existing genotyping and phenotyping data from studies among other Mongoloid populations cannot be implicitly extrapolated on Yakut people. Pharmacogenetic data on individual response to drugs in Yakut patients should be made use of in clinical practice, to develop personalized isoniazid administration algorithms, with a final goal to make treatment more effective and safe.

Rheumatoid arthritis (RA) is a multifactorial incurable immune-inflammatory disease. Progression leads to joint deformation, cartilage and bone tissue destruction, and subsequent disability. The primary goal of RA pharmacotherapy is to achieve disease remission. For this purpose, several classes of drugs are used: basic anti-inflammatory drugs (DMARDs), which are a large group of synthetic and biological drugs that are combined according to their ability to influence the pathogenetic mechanisms of RA; glucocorticoids, which are recommended for use in combination with DMARDs; and non-steroidal anti-inflammatory drugs, which are used to relieve acute and chronic pain. The treatment of RA is a long-term process, and the drugs used for this condition are not always safe and not always effective, which leads to discontinuation of treatment in 20–50 % of patients. Therefore, there is a need to develop new pharmacological targets that can increase drug effectiveness and reduce drug toxicity. One promising therapeutic target is proteinase-activated receptors (PARs), particularly PAR2, whose activation contributes to the occurrence of inflammation, fibrosis, and proliferation of connective tissue. Experiments have demonstrated that inhibition of PAR2 activity prevents the development of RA pathogenesis and positively modifies the course of the disease. The search for drugs that inhibit PAR2 was carried out in the following directions: indirect blockade of PAR2 activity; creation of monoclonal antibodies; search for PAR2 inhibitors among peptide compounds; synthesis of low-molecular-weight inhibitory substances.

Diaphorase (NQO1, NAD(P)H:quinone oxidoreductase 1) is an important biomarker of the presence and progression of cancer and also plays a key role in the activation of prodrugs used in targeted chemotherapy of tumors. This work aimed to compare data from long-term studies of the role of diaphorase in the intracellular activation of prodrugs used in targeted chemotherapy of oncologic diseases. The review includes data from relevant publications describing the biochemical functions of diaphorase, its role in oncology, and possibilities for increasing the effectiveness of antitumor therapy through induction of this enzyme. Articles published from 2000 to 2025 and indexed in the databases PubMed, ScienceDirect, and eLIBRARY.RU were analyzed. The study used methods of internet analysis, content analysis, and historical and descriptive-analytical approaches. Diaphorase accelerates the two-electron reduction of quinones to hydroquinones, preventing the formation of free radicals whereas simultaneously providing bioreductive activation of a number of cytotoxic drugs. Overexpression of diaphorase in malignant cells makes it possible to use this enzyme as a biocatalytic mechanism for selective delivery and activation of prodrugs, thereby increasing therapeutic effectiveness. The review examines modern enzyme–prodrug strategies, including ADEPT (Antibody-Directed Enzyme Prodrug Therapy), GDEPT (Gene-Directed Enzyme Prodrug Therapy), and PMT (Prodrug Monotherapy), as well as prospects for induction of diaphorase by compounds of the 1,2-dithiole-3-thione class and phytochemical agents. The relationship between NQO1 activity, mitochondrial dysfunction of tumor cells, and initiation of apoptosis is emphasized. Overall, diaphorase is considered a promising molecular target for the development of new bioreductive and mitochondria-targeted antitumor drugs.

Objective. To identify new anxiolytics among selective carbonic anhydrase II inhibitors. Materials and methods. The study involved nine new selective carbonic anhydrase II (CAII) inhibitors, which are sulfonamide derivatives with laboratory codes B1–3, B10–13, B18, and B24. The open field, elevated plus maze, and tail suspension tests were used. Two types of animals were examined: mice and rats. Statistical processing was performed using Microsoft Excel and Biostatistics software. Results. Both in experiments on rats and mice, compound B24 exhibits anxiolytic and antidepressant activity, while also enhancing the cognitive functions of animals. Compounds B10, B12, and B18 potentially possess anxiolytic effects, while B13 exhibits antidepressant activity. С onclusion. The study results indicate that new drugs from selective carbonic anhydrase II inhibitors possess anxiolytic and antidepressant activity while improving cognitive functions in animals.

Introduction: Parkinson’s disease (PD) is a chronic neurodegenerative disease of the central nervous system, the pathogenesis of which is associated with the death of dopaminergic neurons of the midbrain substantia nigra. The mainstay of therapy for PD is levodopa. However, in the initial stages of PD or in case of levodopa intolerance, MAO B inhibitors are used. Purpose of the study was to determine antiparkinsonian activity of newly synthesized selective MAO-B inhibitors in vivo on the model of experimental parkinsonism in white mice. Materials and Methods: Parkinsonian syndrome in mice was modeled by systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). As the criteria for its evaluation, we used the determination of muscle rigidity severity by step length of mice and evaluation of oligokinesia severity and emotional and mental disturbances in the open field test. A total of 9 candidate compounds were studied, assigned with laboratory codes S1-S5, S9, S10, S14, and S15. Rasagiline was used as a comparison drug. Results and Discussion: Of the 9 compounds used at a dosage of 2mg/kg, the degree of rigidity was significantly reduced by compounds S1, S9, and S15; locomotor activity was restored to the level reached through rasagiline only by compound S9; the decline in exploratory activity was prevented only by S9 and to some extent by S5. Conclusion: Only compound S9 having benzenesulfonamide chemotype showed significant therapeutic potential in a model of experimental parkinsonism and only in relation to it additional studies can be planned.

The effectiveness and safety of favipiravir may be determined by polymorphisms of genes encoding enzymes involved in the biotransformation of the drug — AOX1 and CYP1A2. The aim of the study was to analyze the distribution frequency of allelic variants of genes encoding enzymes involved in the biotransformation of favipiravir AOX1 (rs55754655 and rs10931910) and CYP1A2*F1 (rs762551) among ethnic groups of the Volga region and the Far East. Material and methods. The study involved 497 volunteers from five ethnic groups: Russians, Mari, Mordvins, Nanai, and Buryats. The definition of belonging to an ethnic group was determined by double self-identification. Biomarker carriage was determined by the RT-PCR method. Results. Statistically significant differences between ethnic groups were observed in relation to the studied single nucleotide polymorphisms. The frequency of occurrence of the mutant allele C rs10931910 AOX1 among the Nanai differs from all ethnic groups except the Buryats, and the minor allele C rs55754655 AOX1 was significantly different among the Mari. A difference was found in the distribution of the A allele of rs762551 CYP1A2*F1 between the Buryat and Russian groups. Distribution patterns corresponded to frequencies in the larger populations from which the studied subpopulations originated. The frequencies of occurrence of the C allele of rs55754655 AOX1 were 10% in Russians, 5% in Mari, 3% in Buryats, 7.5% in Mordvins, 3.5% in Nanai. Allele C rs10931910 AOX1 was detected in 48%, 42%, 86%, 36%, and 77.5%, respectively, polymorphism of the CYP1A2*F1 gene rs762551 (mutant allele — A) — 65%, 55%, 68%, 70%, and 74%, respectively. Conclusion. There is heterogeneity in the distribution of polymorphisms of genes and enzymes that metabolize drugs, including favipiravir, which may be important when personalizing therapy for patients representing certain ethnic groups of the Russian Federation.