Vol. 19 No. 4(76) (2021)

Aim. To demonstrate the advantages of large-scale virtual libraries generated using chemical protocols previously validated in primary steps of the drug discovery process.
Results and discussion. Two validated parallel chemistry protocols reported earlier were used to create the chemical space. It was then sampled based on diversity metric, and the sample was subjected to the virtual screening on BRD4 target. Hits of virtual screening were synthesized and tested in the thermal shift assay.
Experimental part. The chemical space was generated using commercially available building blocks and synthetic protocols suitable for parallel chemistry and previously reported. After narrowing it down, using MedChem filters, the resulting sub-space was clustered based on diversity metrics. Centroids of the clusters were put to the virtual screening against the BRD4 active center. 29 Hits from the docking were synthesized and subjected to the thermal shift assay with BRD4, and 2 compounds showed noticeable dTm.
Conclusions. A combination of cheminformatics and molecular docking was applied to find novel potential binders for BRD4 from a large chemical space. The selected set of predicted molecules was synthesized with a 72 % success rate and tested in a thermal shift assay to reveal a 6 % hit rate. The selection can be performed iteratively to fast support of the drug discovery.

Aim. To analyze and summarize literature data on the state of classification and taxonomy of Iris genus plants of Iridaceae family.
Results and discussion. The genus Iris L. is one of the largest species of Iridaceae Juss family, which includes 1,800 species of 80 genera. Despite the fact that plants are very common as ornamental plants, there is currently no single classification for both horticultural and wild species of Iris genus. Various classifications and systems of irises have been proposed, the main difference between them is related to the understanding of the genus scope. The taxonomy of Iris genus underwent dramatic changes in the last century, especially in recent decades after the introduction of molecular methods. This paper deals with the analysis of current literature data on the existing classifications of Iris genus plants, the correspondence between taxonomic studies and the results of recent molecular studies. The data presented summarize the traditional classifications according to Rodionenko and Matthew, and also describe modern achievements in phylogenetic studies of this genus using functional genomic studies, involving molecular markers in irises.
Conclusions. The data analyzed and summarized in the article can be useful for solving issues of taxonomy, phylogeny, genetics and practical problems of selection of plants of Iris genus; in addition, they will contribute to a more appropriate use of the Iris raw material in practical pharmacy.

Aim. To generalize and systematize information on the properties of modern chemical disinfectants and antiseptic agents (DA and AA) – peroxide compounds, surfactants, salts of heavy metals and metals of variable valence in the highest oxidation state, alcohols, phenols and quaternary ammonium salts.
Results and discussion. The classification of DA and AA by the chemical structure was performed. The spectrum of their activity, directions and forms of DA and AA were given. Toxicity and the impact on the environment were described.
Conclusions. The results of the study conducted allow us to state that modern DA and AA of a wide spectrum of action are peracetic acid and, to a certain extent, hydrogen peroxide. However, they are unstable in dilute solutions. Other reagents are chemically stable, but they are characterized by a weak or average action against spores and viruses. The most effective DA and AA are mixtures
(combinations) of compounds belonging to different classes. The examples of these combinations are “surfactants + biguanidine derivatives”; “quaternary ammonium salts + phenol derivatives”; “surfactants + aldehydes”; “quaternary ammonium salts + hydrogen peroxide”. These mixtures combine the advantages and compensate for the disadvantages of individual DA and AA.

Aim. To develop an alternative method for the quantitative determination of the benzalkonium chloride content as an active pharmaceutical ingredient in the disinfectant solution “CUTASEPT® F”.
Materials and methods. The method is based on the ability of benzalkonium chloride to inhibit the enzymatic hydrolysis of acetylcholine by acetylcholinesterase. The reaction rate is assessed by the non-hydrolyzed acetylcholine residue, which is determined by the amount of peracetic acid produced during the interaction with the excess of the hydrogen peroxide solution. The indicator reaction is the interaction of p-phenetidine with peracetic acid that leads to the formation of 4,4’-azoxyphenetole with λ_max = 358 nm (log₁₀ ε = 4.2).
Results and discussion. As a result of the research conducted the linear dependence of the degree of inhibition of the enzymatic hydrolysis of acetylcholine (U, %) on the concentration of benzalkonium chloride was determined in the concentration range of (0.5 – 7.0) × 10^–6 mol L^-1 with the correlation coefficient of 0.999. The limit of quantitation was 1.9 × 10^–6 mol L^-1.
Conclusions. As a result of the research conducted the kinetic enzymatic method for the quantitative determination of benzalkonium chloride has been developed by its inhibitory effect in the biochemical reaction of acetylcholine hydrolysis. This method is fast, cheap and easy to perform, does not require expensive equipment, and available for use in the field.

Aim. Today, there are a lot of dietary supplements with lingonberry at the pharmaceutical market of Ukraine; therefore, the analysis and quality control of these products are relevant. In this connection, the aim of the research was to study the qualitative composition and determine the quantitative content of phenolic compounds in dietary supplements with lingonberry.
Materials and methods. Such dietary supplements as “Extract of lingonberry” (MEDAGROPROM), “Lingonberry” (Danikafarm), “Lingonberry nano” (LSS SYSTEM) were chosen for the study. The qualitative analysis was performed by thin layer chromatography (TLC), spectrophotometry was used for the quantitative determination.
Results and discussion. Hydroquinone derivatives, flavonoids and hydroxycinnamic acids were found in the dietary supplements analyzed. The total content of phenolic compounds was 8.70, 0.26, 0.30 %, flavonoids – 6.37, 0.15, 0.12 %, hydroxycinnamic acids – 0.94, 0.06, 0.13 %, and hydroquinone derivatives – 1.01, 0.04, 0.03 % in such dietary supplements as “Extract of lingonberry” (MEDAGROPROM), “Lingonberry” (Danikafarm), “Lingonberry nano” (LSS SYSTEM), respectively.
Conclusions. The qualitative and quantitative analysis of the dietary supplements with lingonberry analyzed has been performed. “Extract of lingonberry” (MEDAGROPROM) dietary supplement meets the requirements of the State of Pharmacopoeia of Ukraine 2.0, whereas “Lingonberry” (Danikafarm) and “Lingonberry nano” (LSS SYSTEM) do not. Based on the results of the study it can be concluded that the problem of compliance of dietary supplements is relevant today and requires the introduction of regulatory documentation for the detection and determination of biologically active substances in dietary supplements.

Aim. To determine the value of the antioxidant activity of the biomass and culture fluid extracts of strains of seven species of Pholiota genus: P. adiposa, P. alnicola, P. aurivella, P. limonella, P. nameko, P. squarrosa, P. subochracea, which stored in the Mushroom Culture Collection (IBK) of the M. G. Kholodny Institute of Botany of the National Academy of Sciences of Ukraine.
Materials and methods. The antioxidant properties of the biomass and culture fluid extracts of strains of Pholiota genus were determined by the method of Elfahri et al. using DPPH (1,1-diphenyl-2-picrylhydrazyl). Mycelia of the strains studied were grown by the surface method on a liquid glucose-pepton-yeast medium. The culture fluid was separated from the mycelial biomass by filtration through a capron filter. The absorption of methanol extracts of the culture fluid and the biomass of the strains studied was measured at 517 nm on a SF 46 LOMO spectrophotometer.
Results and discussion. Comparing the data obtained we can conclude that the antioxidant effect is significantly higher in the case of methanol biomass extracts – the indicators ranged from 65.98 ± 0.98 % (P. nameko) to 83.6 ± 1.4 % (P. alnicola). As for the culture fluid extracts, the maximum values were recorded in the case of P. limonella (38.3 ± 1.14 %), and the minimum values were observed for P. subochracea (7.37 ± 0.46 %).
Conclusions. For the first time, the value and limits of variation in the antioxidant activity of the biomass (65-83 %) and culture fluid extracts (7.4-38 %) have been determined for strains of medicinal fungal species P. adiposa, P. alnicola, P. aurivella, P. limonella, P. nameko, P. squarrosa, P. subochracea.

Aim. To determine the quantitative content of total polyphenols and the amount of hydroxycinnamic acids in the series of tinctures from rhizomes with roots of Rumex confertus Willd., Sanguisorba officinalis L., roots of Rosa majalis Herrm., Rosa canina L., Arctium lappa L., Arctium minus (Hill) Bernh., Arctium tomentosum Mill., and the herb of Bidens tripartita L.
Materials and methods. As study objects the tinctures from rhizomes with roots of Rumex confertus, Sanguisorba officinalis, roots of Rosa majalis, Rosa canina, Arctium lappa, Arctium minus, Arctium tomentosum and the herb of Bidens tripartita were used. These tinctures were obtained by the method of maceration at room temperature and the ratio of 1 : 5 of the plant raw material/finished products; the extractant was 50 % ethyl alcohol. The quantitative content of total polyphenols and the amount of hydroxycinnamic acids was determined by spectrophotometry according to the methods of the State Pharmacopoeia of Ukraine.
Results and discussion. The limits of the quantitative content of total polyphenols and the amount of hydroxycinnamic acids in the tinctures were determined. They were not less than 0.070 mg mL^-1 and 0.002 mg mL^-1 for the tincture of rhizomes with roots of Rumex confertus, 0.100 mg mL^-1 and 0.005 mg mL^-1 for the tincture of rhizomes with roots of Sanguisorba officinalis, 0.070 mg mL^-1 and 0.002 mg mL^-1 for the tincture of Rosa majalis roots, 0.080 mg mL^-1 and 0.001 mg mL^-1 for the tincture of Rosa canina roots, 0.01 mg mL^-1 and 0.001 mg mL^-1 for the tincture of Arctium lappa roots, 0.010 mg mL^-1 and 0.002 mg mL^-1 for the tincture of Arctium minus roots, 0.001 mg mL^-1 and 0.002 mg mL^-1 for the tincture of Arctium tomentosum roots, 0.070 mg mL^-1 and 0.001 mg mL^-1 for the tincture of Bidens tripartita herb, respectively.
Conclusions. The quantitative content of total polyphenols and the amount of hydroxycinnamic acids in tinctures from rhizomes with roots of Rumex confertus, Sanguisorba officinalis, roots of Rosa majalis, Rosa canina, Arctium lappa, Arctium minus, Arctium tomentosum and the herb of Bidens tripartita have been determined. The data obtained will be used in further work on the study of tinctures of these types of the plant raw material.

Aim. To select the optimal extractant for the extraction of a number of groups of phenolic compounds from Lаurus nоbilis L. leaves based on the determination of the quantitative content of these groups in the extracts obtained.
Materials and methods. Lаurus nоbilis L. leaves were harvested in November 2020 from artificially cultivated specimens aged 5 – 7 years. The quantitative determination of polyphenols was performed using the spectrophotometric method at a wavelength of 760 nm in accordance with the requirements of the Supplement of the State Pharmacopoeia of Ukraine (SPhU) 1.2 (2.8.14). The quantitative content of this group of compounds was calculated with reference to pyrogalol and dried substance. The quantitative determination of the amount of hydroxycinnamic acids was performed according to the SPhU 2.2 monograph “Orthosyphon stamen (kidney tea) leaves^N” by the spectrophotometric method at a wavelength of 505 nm and calculated with reference to rosmarinic acid. The quantitative determination of the amount of flavonoids was performed according to the SPhU 2.0 monograph “Hawthorn leaves and flowers” by the spectrophotometric method at a wavelength of 410 nm and calculated with reference to hyperoside.
Results and discussion. The analysis of the results for the quantitative determination of polyphenols, the amount of hydroxycinnamic acids and the amount of flavonoids in extracts from Lаurus nоbilis L. leaves obtained using water, water-ethanol mixtures and 96 % ethanol showed that 70 % ethanol was optimal for extracting compounds of these groups. The quantitative content of polyphenols (calculated with reference to pyrogalol) was not less than 21 %, the amount of hydroxycinnamic acids (calculated with reference to rosmarinic acid) – not less than 3 %, the amount of flavonoids (calculated with reference to hyperoside) – not less than 5 %.
Conclusions. For the first time, the quantitative content of a number of groups of phenolic compounds (polyphenols, the total amount of hydroxycinnamic acids, and the total amount of flavonoids) in Lаurus nоbilis L. leaves extracts obtained using various extractants has been determined. On this basis, the optimal extractant – 70 % ethanol for the extraction of phenolic compounds has been selected. The results obtained will be used when developing the technology for obtaining substances from Lаurus nоbilis L. leaves.