A crucial direction in the progress of modern medical chemistry is the development and improvement of theoretical investigation methods of drugs mechanisms of action, predicting their activity, and virtual design of new drugs. This review describes the history of targeted search for biologically active compounds, current in silico approaches and tools used in the rational design of potential drugs, in particular the main computational strategies used in modern drug design are presented and outlines the main methodologies for implementing these strategies. 

A range of hybrid molecules incorporating the ciminalum moiety in the thiazolidinone ring demonstrate significant anticancer and antimicrobial properties. Therefore, the aim of our study was to evaluate the properties and mechanism of action of two 4-thiazolidinone-based derivatives, i.e., 3-{5-[(Z,2Z)-2-chloro-3-(4-nitrophenyl)-2-propenylidene]-4-oxo-2-thioxothiazolidin-3-yl}propanoic acid (Les-45) and 5-[2-chloro-3-(4-nitrophenyl)-2-propenylidene]-2-(3-hydroxyphenylamino)thiazol-4(5H)-one (Les-247). In our study, we analyzed the impact of Les-45 and Les-247 on metabolic activity, caspase-3 activity, and the expression of genes and proteins related to inflammatory and antioxidant defenses and cytoskeleton rearrangement in healthy human fibroblasts (BJ) and a human lung carcinoma cell line (A549). The cells were exposed to increasing concentrations (1 nm to 100 μM) of the studied compounds for 24 h and 48 h. A decrease in the metabolic activity in the BJ and A549 cell lines was induced by both compounds at a concentration range from 10 to 100 μM. Both compounds decreased the mRNA expression of NRF2 (nuclear factor erythroid 2-related factor 2) and b-actin in the BJ cells. Interestingly, a significant decrease in the level of NF-kB gene and protein expression was detected in the BJ cell line, suggesting a direct impact of the studied compounds on the inhibition of inflammation. However, more studies are needed due to the ability of Les-45 and Les-247 to interfere with the tubulin/actin cytoskeleton, i.e., a critical system existing in eukaryotic cells.

UDC: 615.277.3:547.76].012:542.9

In vitro study and characterization of anticancer activity of new heterocyclic derivative N(5methyl[1,3,4]thiadiazol2yl)propionamide. Methods. The cell culture; MTT assay. Results. We synthesized N(5methyl[1,3,4]thiadiazol2yl)propionamide, which possessed diuretic, cardioprotective, and anti-inflammatory effects. Here, we investigated its cytotoxicity effect towards the tumor cell lines of various tissue origins: liver (HepG2), breast (MCF 7), lung (A549), cervical (KB3 1), and leukemia (HL 60) cells, as well as towards the non-tumor cells (НЕК293 and NIH3T3). The IC50 values of the synthesized compound for tumor cells were in the range of 9.4–97.6 μg/mL. We found that the human hepatocellular carcinoma HepG2 cells were the most sensitive to the action of N(5methyl[1,3,4]thiadiazol 2yl)propionamide with the IC 50 value of 9.4 μg/mL. The studied derivative slightly inhibited the growth of the pseudo normal HEK293 and NIH3T3 cells. Conclusions. The anti prolife rative activity of N(5methyl[1,3,4]thiadiazol2yl)propionamide dropped in the order: hepatocarcinoma > leukemia > breast carcinoma cells. Thus, we revealed in the molecule of N(5methyl[1,3,4]thiadiazol2yl)propionamide a combination of the diuretic, cardioprotec tive, anti-inflammatory and anticancer activities, which is of great significance for this agent
as a potent anticancer medicine

Fungi of the genus Lactarius Pers. before the maturation of spores are not damaged by microorganisms, insects, mollusks, and animals. Such resistance correlates with the period when the basidiomes of these fungi are filled with milky juice, which contains substances of various chemical nature that provide their protection. </jats:sec> <jats:sec> Objective: The aim of our work is to present the results of our recent and previously published studies on the identification and toxicological characteristics of substances available in the milky juice of fungi of the genus Lactarius Pers and used for protection against predator and parasite organisms. The possibility of using these substances to suppress tumor cells is also discussed. </jats:sec> <jats:sec> Methods: The biological effect of the juice of L. pergamenus, L. quietus, and L. volemus, as well as methylene chloride, extracts obtained from fresh, frozen and dried basidiomes of L. pergamenus was studied. Purification of individual fractions of hexane extract from the basidiomes was performed by chromatography on a silica gel column and their analysis by done by thin layer chromatography and gas chromatography mass spectrometry. </jats:sec> <jats:sec> Results: The sesquiterpene aldehydes were shown to be the main component of the chemical protection system of Lactarius. These agents are present in the milky juice of the Lactarius fungi, and they are easily oxidized by oxygen in the air. The milky juice of these mushrooms is also rich in higher fatty acids and phthalates. Phthalates possess an insecticidal effect, while higher fatty acids are capable of forming adducts with sesquiterpenes that provide emulsion stability. Water-soluble substances, in particular, the polyphenol oxidase enzyme, whose activity correlates with the content of milky juice in basidiomes, also play a protective role. </jats:sec> <jats:sec> Conclusion: Milky juice of mushrooms of Lactarius Pers. genus is a stable balanced emulsion containing a large number of substances. One part is responsible for the toxic effects on other organisms, while the other part determines the chemical stability of the emulsion. Altogether, they create an effective system of protection of fungi of the Lactarius genus against microorganisms, insects, mollusks, and animals. 

Chitosan is a cationic polymer capable of binding acidic drugs. In addition, it has haemostatic and antimicrobial activity. Chitosan derivatives withanti-fibrinolytic properties may present increased effectiveness, especially when the added substance forms an adduct with chitosan. The aim of this work was to study the haemostatic action of the chitosan–tranexamic acid complex. Two chitosan solutions (molecularweight of 250 and 625 kDa at pH 5.7 and 6.2, and after tranexamic acid had been added to chitosan solutions) werestudied. Haemostatic evaluation was performed on white outbred mice. The time to complete cessation of bleeding from the tail was determined. Chitosan 625 kDa at pH 6.2 had the best haemostatic properties. Adding tranexamic acid to the chitosan solution reduced the bleeding time. This phenomenon was more pronounced for chitosan 625 kDa. Compared with control animals, this chitosan reduced bleeding arrest time by 30% and the chitosan–tranexamic acid adduct reduced the bleeding arrest time by 75%.