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. 

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

UDC: 615.277.3:547.78].012:542.9

In vitro study and characterization of anticancer activity of heterocyclic derivative — [3-allyl-4-(41-methoxyphenyl)-3H-thiazole-2-ylidene]-(32-trifluoromethylphenyl)amine hydrobromide

Phenolformaldehyde resins were obtained by polycondensation of concentrated phenols with formaldehyde in the presence of hydrochloric acid. Concentration of phenols is carried out by treating the phenolic fraction of coal tar with an aqueous solution of sodium hydroxide followed by neutralization of water-soluble phenolates with hydrochloric acid. The kinetic dependences of resin yield and softening temperature on the duration of the process at 333, 353, and 373 K were obtained. The order of the reaction was determined and the effective activation energy of this process was determined by a graphical method. In the interval 333-373 K for polycondensation reactions, the equation of the dependence of the resin yield on the temperature and duration of the process was obtained.

Following the interaction of 2-chloro-N-(5-aryl-1,3,4-oxadiazole-2-yl) acetamides 1a-b with ammonium thiocyanate in dry acetone, the 5-unsubstituted 2-imino-4-thiazolidinones 4a-b have been synthesized. Compounds 4a-b were subsequently utilized in Knoevenagel condensation with aromatic aldehydes or isatin derivatives to synthesize the series of 5-arylidene/isatinylidene substituted 2-(1,3,4-oxadiazol-2-yl)imino-4-thiazolidinones 5a-h and 6a-d. The structures of target compounds were confirmed by using 1H NMR spectroscopy and elemental analysis. Evaluation of anti-cancer activity in
vitro for the synthesized compounds was performed following the National Cancer Institute protocol against leukemia, melanoma, lung, colon, CNS, ovarian, renal, prostate, and breast cancer cell lines. As a result, the most active compound 5a, namely 2-[5-(4-chlorophenyl)-[1,3,4]oxadiazol-2-ylimino]-5-(4-methoxybenzylidene)thiazolidin-4-one was found to be a highly efficient anti-tumor candidate with average logGI50 and logTGI values of -5.19 and -4.09, respectively