The rapid development in bacterial resistance to many groups of known antibiotics forces the researchers to discover antibacterial drug candidates with previously unknown mechanisms of action, one of the most relevant being the inhibition of tRNA (Guanine37-N1)-methyltransferase (TrmD). The discovery of selective TrmD inhibitors in the series of carboxamide derivatives of thienopyrimidines became a background for further modification of the similar structures aimed at the development of promising antibacterial agents. As part of this research, we carried out the construction of heterocyclic hybrids bearing the moieties of thieno[2,3-d]pyrimidine and benzimidazole starting from 3,5-dimethyl-4-oxo-2-thioxo-1H-thieno[2,3-d]pyrimidine-6-carboxylic acid, which was used as the pivotal intermediate. The hybrid molecule of 6-(1H-benzimidazol-2-yl)-3,5-dimethyl-2-thioxo-1H-thieno[2,3-d]pyrimidin-4-one prepared via condensation of the carboxylic acid with ortho-phenylenediamine was further alkylated with aryl/hetaryl chloroacetamides and benzyl chloride to produce the series of S-alkyl derivatives. The results of molecular docking studies for the obtained series of S-alkyl benzimidazole-thienopyrimidines showed their high affinity to the TrmD isolated from the P. aeruginosa. The results of antimicrobial activity screening revealed the antimicrobial properties for all of the studied molecules against both Gram-positive and Gram-negative bacteria and the Candida albicans fungal strain. The highest antimicrobial activity was determined for 2-{[6-(1H-benzimidazol-2-yl)-3,5-dimethyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-2-yl]thio}-N-(4-isopropylphenyl)acetamide, which also had the highest affinity to the TrmD inhibitor’s binding site according to the docking studies results.

According to the World Journal of Gastroenterology, more than 5 million people worldwide suffer from inflammatory bowel disease. The use of phytotherapeutic remedies in treatment of chronic inflammatory processes can be an effective alternative in patient’s therapy. The advantage of herbal medicines is the ability to influence various links of pathogenesis, lack of addiction, and the absence of withdrawal syndrome with long-term use in chronic pathology. In order to develop a new combined remedy with anti-inflammatory activity for the treatment of colitis, thirteen herbs, which are used in official or traditional medicine in inflammatory processes, were selected among the Ukrainian flora members. To select the most promising drugs and optimize further pharmacological research, molecular docking of the main active substances of the selected herbs to the fundamental pro-inflammatory enzymes – lipoxygenase-5 (LOX-5) and cyclooxygenase-2 (COX-2) – was carried out. Native inhibitors AKBA and celecoxib, respectively, were used as the reference ligands. The selection of candidate structures for in silico research was carried out according to the bibliosemantic research and logical-structural analysis concerning anti-inflammatory effect of the substances, which are part of chemical composition of the selected herbs. Molecular docking results have shown a high affinity level for the active site of the LOX-5 inhibitor gallotannin, quercetin, inulin, sitosterine, and moderate for ellagic acid. High affinity level for the active site of the COX-2 inhibitor was found for inulin, quercetin, gallotannin, ellagic acid and urticin A, moderate one – for gallic acid. For the further pharmacological in vitro and in vivo studies for anti-inflammatory activity, medicinal herbs with the highest content of the mentioned compounds were selected: Inula helenium, Cichorium intybus, Capsella bursa-pastoris, Foeniculum vulgare, Equisetum arvense, Veronica officinalis. Besides, it is recommended to use aqueous extracts of the selected herbs for the further pharmacological studies.

Pineapple weed (Matricaria discoidea DC.) is a widespread plant in Europe and North America. In ethnomedicine, it is well-known for its anti-inflammatory and spasmolytic activities. The aim of this research was to develop novel methods of M. discoidea processing to obtain essential oil and dry extracts and to investigate their phytochemical compositions. Moreover, the molecular docking of the main substances and the in vivo studies on their soporific and analgesic activities were conducted. The essential oil and two dry extracts from M. discoidea were prepared. A total of 16 phenolic compounds (seven flavonoids, seven hydroxycinnamic acids, and two phenolic acids) in the dry extracts were identified by means of UPLC-MS/MS. In the essential oil, nine main terpenoids were identified by gas chromatography (GC). It was shown that phenolic extraction from the herb was successful when using 70% ethanol in a triple extraction method and at a ratio of 1:14–1:16. The in vivo studies with rodents demonstrated the analgesic activity of the M. discoidea extracts and improvements in the sleep of animals. The dry extracts of M. discoidea did not show any toxicity. The molecular docking analysis showed a high probability of COX-1,2 inhibition and NMDA receptor antagonism by the extracts.

The search for neuroprotective compounds in lavender is driven by its traditional use for brain health, with antioxidant activity serving as a key mechanism in reducing oxidative stress and supporting cognitive function. Lavender’s potential to protect neurons is based on its calming, anti-stress properties, which increase the brain’s resistance to neurodegeneration. Although lavender is not a traditional medicinal plant in Ukraine, it is increasingly recognised for its medicinal properties and is widely cultivated in the country. Lavender use in Ukraine is influenced by both global herbal practices and local medical traditions. The aim of this study was to optimise the preparation of lavender herb extracts, perform chemical profiling and evaluate their antioxidant and neuroprotective activities. The study focused on Lavandula angustifolia cultivated in Lviv, Ukraine. Modern analytical methods were used, including HPLC, spectrophotometry, molecular docking, lyophilisation and pharmacological testing. The selection of the optimal conditions for obtaining lavender herb extracts was determined on the basis of the results of the total yield of phenolic compounds in each extract, where it was found that the raw material–solvent ratio (1:10) in water and 50% ethanol gave the highest yield of substances; the preferred extraction time was 20 min, and the temperature was 60–70 °C, especially for water extraction. Further HPLC analysis identified marker compounds including rosmarinic acid (28.31 mg/g), chlorogenic acid (1.64 mg/g) and luteolin (0.23 mg/g) in the lyophilised ethanol extract, which were previously recognised as neuroprotective markers by molecular docking. The water extract showed higher antioxidant (total 50.85 mg/g) and neuroprotective activity, probably due to synergistic interactions among the components. Behavioural tests further demonstrated the neuroprotective potential of lavender herb. These results demonstrate the potential neuroprotective activity of lavender herb and open new possibilities for its use in the treatment of various neurodegenerative diseases.

Compounds with thieno[2,3-d]pyrimidine core modified with amide group at position five of the heterocyclic system were reported as ligands to bacterial TrmD, which is an enzyme responsible for protein synthesis in bacterial cells and its blockage leads to the death of bacteria or makes them less resistant to antibiotic therapy. The great problem of antibiotic resistance, especially of Gram-negative bacteria like Pseudomonas aeruginosa, forced us to design and study the antimicrobial properties of novel thieno[2,3-d]pyrimidine with amide function at position six as possible bacterial TrmD inhibitors. For the synthesis of the target derivatives with an aromatic pyrimidine cycle and a methyl group at position four, the Suzuki reaction was used. The previously unknown key intermediate 4,5-dimethylthieno[2,3-d] pyrimidine-6-carboxylic acid was further transformed into various novel derivatives of 4-methylthieno[2,3-d] pyrimidines by interaction with amines. The antimicrobial activity screening results show that benzyl amides of 4,5-dimethylthienopyrimidines were the most active, especially against Ba?illus subtilis and P. aeruginosa. The docking studies also revealed that benzylamides showed the best binding parameters to the selective inhibitors’ active site of tRNA (Guanine37-N1)-methyltransferase, an enzyme isolated from P. aeruginosa.