UDC 547-327:547.821:54.057

The aim. The combination in one molecule of pharmacophore fragments of thieno[2,3-d]pyrimidine-4-carboxylic acids with the fragments of 2-or 4-aminopyrimidine by peptide coupling promoted acylation in order to develop the new drug-like molecules with antimicrobial activity. Materials and methods. The molecular docking studies were performed with the AutoDock Vina and AutoDock-Tools 1.5.6 programs; TrmD Pseudomonas aeruginosa PDB ID – 5ZHN was used as the protein target. Synthetic methods of peptide coupling were used. 1H and 13C NMR spectra were recorded with a Varian-400 spectrometer at 400 MHz and Bruker Avance DRX 500 device at 500 MHz and 125 MHz in DMSO-d6 as a solvent, using TMS as the internal standard. LC-MS analysis of the compounds was carried out with Agilent 1100 HPLC з with at-mospheric pressure chemical ionization (APCI). The studied derivates were tested in vitro for their antibacterial and anti-fungal activities using agar diffusion and serial dilutions resazurin-based microdilution assays (RBMA). Results and discussion. By the combination of the pharmacophore fragments of thieno[2,3-d]pyrimidine-4-carboxylic acids with the fragments of 2-of 4-aminopyrimidine, the combinatorial library of amides was constructed. For this library of compounds, the potential of antimicrobial activity was revealed using docking studies to the TrmD enzyme isolated from P. aeruginosa. The peptide coupling promoted by 1,1’-carbonyldiimidazole was found to be effective for the synthesis of pyridyl amides of thieno[2,3-d]pyrimidine-4-carboxylic acids, and it allowed to combine these phar-macophores in one molecule. The results of antimicrobial activity study revealed the broad spectrum of antimicrobial activity for N-(pyridin-4-yl)-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidine-4-carboxamide (2g), while 5,6-di-methyl-N-(6-methylpyridin-2-yl)thieno[2,3-d]pyrimidine-4-carboxamide (2c) showed the best MIC value against the reference strain of Pseudomonas aeruginosa ATCC 10145. N-(6-Methylpyridin-2-yl)-5,6,7,8-tetrahydro[1]benzothien-o[2,3-d]pyrimidine-4-carboxamide (2h) was also found to be active against Pseudomonas aeruginosa. Conclusions. An effective method for the synthesis of pyridyl amides of thieno[2,3-d]pyrimidine-4-carboxylic acid has been developed. The amides molecular docking method showed their ability to inhibit TrmD enzyme isolated from P. aeruginosa; the further in vitro studies of the compounds showed the rationality of the further studies of the derivatives with 2-ami-no-6-methylpyridine in amide substituent because this fragment favoured the selectivity against Pseudomonas aeruginosa. © The Author(s) 2023.

The analysis presented in this article is a continuation of a broader qualitative study examining the composition of the chloroform fraction of Caltha palustris. The study discovered 29 compounds, and 26 of them have been identified:paraffinic hydrocarbons, esters, fatty aldehydes, morphine derivatives, thiazole derivatives, benzodiazepines, naphthalene, and a small amount of terpene. It was figured out that the investigated lipophilic extract has an antioxidant impact. For the investigation, there were used such assays as the DPPH radical and the ABTS radical cation assays. Moreover the investigated lipophilic extract has an antimicrobial activity both in terms of gram-positive (Staphylococcus aureus (ATCC 25923 (F-49)), Bacillus cereus 34 (non-MDR), Enterococcus faecalis 26(MDR) and gram-negative, (Raoultella terrigena (ATCC 33257), Escherichia coli (ATCC 25922), Escherichia coli 168) microorganisms and yeast Candida spp. In addition, the significant content of biologically active substances in the lipophilic volatile fraction of Caltha palustris indicates the prospects for further study. © 2023, Research Journal of Pharmacy and Technology. All rights reserved.

UDC 615.322:615.451.1

Actuality. The widespread use of herbal drugs with anti-inflammatory and nephroprotective properties stimulates the search for new active biological substances. Of particular interest are plants from the Ranunculaceae family, especially Anemone nemorosa, which contains a range of potentially bioactive components such as anemonin, protoanemonin, and others. Understanding the acute toxicity, anti-inflammatory, and hypoazotemic activity of Anemone nemorosa extracts opens possibilities for the development of new therapeutic agents based on this plant. Materials and methods. Ethanol extracts were obtained from the aerial parts of Anemone nemorosa harvested during the flowering period. The study included the examination of oral acute toxicity conducted on Wistar rats over 14 days, anti-inflammatory activity using the carrageenan-induced paw edema method in Wistar rats, and hypoazotemic activity on models of healthy and acute renal failure in Wistar rats. Results. The extracts showed no acute toxicity at the administered dose. It was established that the oral administration of the extracts is non-toxic up to a dose of 200 mg/kg body weight. The anti-inflammatory tests did not reveal significant therapeutic effects. However, the hypoazotemic tests demonstrated a reduction in blood urea and creatinine levels, and an increase in these indicators in urine, especially under conditions of acute renal failure, indicating a strong diuretic effect of the extracts. Conclusions. The Anemone nemorosa extracts exhibited strong hypoazotemic and diuretic activity, which may be beneficial for the treatment of kidney diseases. The absence of anti-inflammatory activity requires further analysis and possible modification of extraction methods. The study results support the potential use of this plant in developing new nephroprotective phytopreparations. © O. Khropot, Yu. Konechnyi, G. Lavryk, I. Tymchuk, O. Pinyazhko, V. Lubenets, R. Konechna.

In the literature, the chemical composition of Rhododendron tomentosum is mainly represented by the study of isoprenoid compounds of essential oil. In contrast, the study of the content of flavonoids will contribute to the expansion of pharmacological action and the use of the medicinal plant for medical purposes. The paper deals with the technology of extracts from Rh. tomentosum shoots using ethanol of various concentrations and purified water as an extractant. Extracts from Rh. tomentosum were obtained by a modified method that combined the effects of ultrasound and temperature to maximize the extraction of biologically active substances from the raw material. Using the method of high-performance thin-layer chromatography in a system with solvents ethyl acetate/formic acid/water (15:1:1), the following substances have been separated and identified in all the extracts obtained: rutin, hyperoside, quercetin, and chlorogenic acid. The total polyphenol content (TPC) and total flavonoid content (TFC) were estimated using spectrophotometric methods involving the Folin-Ciocalteu (F-C) reagent and the complexation reaction with aluminum chloride, respectively. A correlation analysis was conducted between antioxidant activity and the polyphenolic substance content. Following the DPPH assay, regression analysis shows that phenolic compounds contribute to about 80% (r² = 0.8028, p < 0.05) of radical scavenging properties in the extract of Rh. tomentosum. The extract of Rh. tomentosum obtained by ethanol 30% inhibits the growth of test cultures of microorganisms in 1:1 and 1:2 dilutions of the clinical strains #211 Staphylococcus aureus and #222 Enterococcus spp. and the reference strain Pseudomonas aeruginosa ATCC 10145. © 2024 by the authors.