Vol. 21 No. 1 (2023)

Aim. DNA-encoded libraries technologies (DELT) are gradually becoming an important part of standard drug discovery toolbox. DELT is looking to find its place between classic low-molecular-weight drug candidates on the one hand, and high-molecular-weight antibodies and peptides on the other hand. On its natural path to overcoming the “childhood diseases” typical for every novel technology, DELT has reached a point where the chemical diversity of DNA-encoded libraries (DELs) becomes an important factor to look out for. In this paper, we aim to take a closer look at the chemical diversity of DELs in their present state and find the ways to improve it.
Results and discussion. We have identified the DEL-viable building blocks from the Enamine Ltd. stock collection, as well as from Chemspace Ltd. virtual collection, using the SMARTS set, which takes into account all the necessary structural restrictions. Using modern cheminformatics tools, such as Synt-On, we have analyzed the scaffold diversity of both stock and virtual core bi- and tri-functional building blocks (BBs) suitable for DNA-tolerant reactions. The identification of scaffolds from the most recently published on-DNA heterocyclization reactions and analysis of their inclusion into the existing BBs space have shown that novel DNA-tolerant heterocyclizations are extremely useful for expanding chemical diversity in DEL technologies.
Conclusions. The analysis performed allowed us to recognize which functional groups should be prioritized as the most impactful when the new BBs are designed. It is also made clear that the development of new DNA-tolerant reactions, including heterocyclizations, have a significant potential to further expand DEL molecular diversity.

1,2,3,4-Tetrahydroisoquinoline (THIQ) is a common scaffold of many alkaloids isolated from several plants and mammalian species. THIQ derivatives possess a broad spectrum of biological activities, including antitumor, antitubercular, antitrypanosomal, antibacterial, anti-HIV, anti-inflammatory, anti-Alzheimer, and anticonvulsant ones.
Aim. To cover updated studies on the biological properties of THIQ derivatives, as well as their structure-activity relationship (SAR), in order to highlight the effect of diverse functional groups responsible for the manifestation of the desired activity.
Results and discussion. We have presented the review on biological activities of THIQ. The SAR studies show that the electron-donating, electron-withdrawing and some heterocyclic functional groups on the backbone plays a vital role in modulating the biological potential of the compounds synthesized.
Conclusions. This review will help pharmaceutical researchers to synthesize novel and potent compounds containing THIQ scaffold.

Aim. The research is aimed at determining the qualitative and quantitative content of essential oils in the aerial part of two species of the genus Pycnanthemum Michx. (Lamiaceae) – P. virginianum (L.) T. Durand & B.D. Jacks. ex B.L. Rob & Fernald and P. californicum Norr. exDurand. The plants were introduced in the M. M. Gryshko National Botanical Garden of National Academy of Sciences of Ukraine (Forest-Steppe zone). These are representatives of the flora of North America, and they are little known in Ukraine. Plants have useful medicinal and nutritional properties, but the biochemical composition of their essential oils has not been sufficiently studied in the world.
Materials and methods. In the experiment, the aerial herbal part of plants collected during the flowering phase was used. The quantitative content of the essential oil was determined by the hydrodistillation method, and its qualitative characteristics were found by the GC-MS analysis. The chromatographic profile was obtained on an Agilent Technologies 7890. The component composition of the essential oil was determined on a gas chromatograph with a HP 6890 mass spectrometric detector with a mass spectrometric detector 5973. We used a mass spectrometric detector 1.6 – 800 a.o.m., EI ionization, SIM & Scan mode, “Hewlett Packard”, USA. Identification of essential oil components was performed using the NIST mass spectrum library in combination with AMDIS content-time identification programs.
Results and discussion. P. virginianum was found to produce 1.96 ± 0.17 % of essential oil, in which 12 compounds out of 13 were identified; P. californicum had 2.66 ± 0.13 % of essential oil, 13 compounds out of 15 were identified. The essential oil samples obtained have pulegone as the dominant component: P. virginianum – 44.65 %, P. californicum – 86.07 %. In addition to it, they also contain thymol, myrcene, 1.8-cineole, menthone, limonene and other compounds.
Conclusions. For the first time, the qualitative and quantitative composition of the essential oils of plants of P. virginianum and P. californicum species introduced in Ukraine has been determined. The results obtained indicate that when introduced plants have a high biosynthesizing ability to produce essential oil. Pulegone has been found to be the dominant component; therefore, the essential oil can be classified as a pulegone-type essential oil. We believe that the raw material of P. virginianum and P. californicum are potentially suitable for use in perfumery, cosmetics, aromatherapy, personal care products, dentistry, and in the pharmaceutical and food industries.

The Kazakhstan flora is rich in promising poorly-studied plants, which are traditionally used in folk medicine, but their introduction into medical practice requires additional in-depth research using modern scientific methods. Alfredia nivea KAR&KIR of the Asteraceae family, which is used in folk medicine as a neurotropic agent, is an interesting object for introduction into official medical and pharmaceutical practice.
Aim. To create new medicines based on Alfredia nivea herb, it is necessary to develop methods for quality control of this raw material, therefore, the aim of the research was to determine the parameters for standardization of the Alfredia nivea KAR & KIR. herb.
Materials and methods. The study objects were samples of the A. nivea herb collected in Kungei Alatau, 4.3 km southeast of the Karabulak village, Eastern Karabulak canyon, Almaty Region, Kazakhstan. The macroscopic and microscopic studies of the A. nivea herb were performed according to the methodology of the European pharmacopeia (EuPh) 2.8.23 “Microscopic examination of the medicinal plant raw material”. The macroscopic studies were performed using a magnifying glass and a MBS-9 binocular microscope, the microscopic studies were done using MS Microscopes 10 (oculars X5, X10, X15, lenses x10,
x40), Micromed XS-4130 (oculars WF15X, lenses x40/0.65, x10/0.25) with a microphotonozzle (China). Identification of the main substances was carried out by the TLC method, testing and the quantitative determination of the flavonoid content were performed according to the EuPh methods.
Results and discussion. Morphological and anatomical features of the A. nivea herb have been determined; on their basis Identifications A and B have been proposed; TLC Identification C of the main BAS of the raw material has been developed; indicators of purity tests have been determined. It has been proposed to carry out the quantitative determination by the content of flavonoids.
Conclusions. The parameters of the A. nivea herb standardization have been determined on the basis of the following indicators: macroscopic and microscopic features, TLC identification of the main BAS of the raw material (hyperoside, rutin, quercetin and chlorogenic acid), related impurities (not more than 2 %), stems with a diameter of more than 20 mm (not more than 10 %), the loss on drying (not more than 13 %), the total ash (not more than 10 %) and at least 0.5 % flavonoids calculated with reference to rutin.

Aim. Using in silico technologies to search for potential SARS-CoV-2 inhibitors among novel tetracyclic ring systems, which are the common core of Crinipellin.
Materials and methods. The study object was new compounds previously synthesized via oxidative dearomatization of Crinipellin A. The method of the flexible molecular docking was applied in the study.
Results and discussion. Using the molecular docking, the affinity of five compounds for the receptor-ACE2 SARS-CoV-2 (PDB ID: 7DF4), a spike protein SARS-CoV-2 (PDB ID: 1WNC), a PL protein SARS-CoV-2 (PDB ID: 7CJD) and a reverse transcriptase enzyme SARSCoV-2 (PDB ID: 6YYT) was studied. The results of the molecular docking obtained suggest that 8,8-dimethyl-5-(phenylsulfonyl)-3,3a,4,5,8,9-hexahydroindeno[3a,4-b]furan-2(7H)-one may be a potential SARS-CoV-2 inhibitor; it is the basis for its further experimental pharmacological study.
Conclusions. The study constitutes one of the stages of searching for SARS-CoV-2 inhibitors. According to the results obtained, a way to search for potential SARS-COV-2 inhibitors based on Crinipellin A derivatives was proposed. Using the most promising compound with hexahydroindeno[3a,4-b]furan core further studies open up another direction for searching for compounds of SARS-COV-2 inhibitors and will save time and laboratory animals while conducting targeted experimental research.