Introduction. Ovarian cancer is one of the most common gynecological cancers worldwide, which is difficult to diagnose and treat. the high mortality rate from ovarian cancer makes the development of new therapeutic drugs relevant. Ribavirin (RBV), commonly used antiviral agent, revealed the anticancer potential, however, it led to the development of severe side effects as well. RBV derivatives were previously synthesized and tested as putative anticancer drugs in the models of hematological malignancies. The aim of this study was to estimate the anticancer effects of and RBV derivatives (MGs) in ovarian cancer cells in vitro. Material and Methods. Cytotoxic and cytostatic effects of the MGs on ovarian cancer cells (OVCAR3 and OVCAR4) were assessed using the MTT assay and cell counting with trypan blue staining. distribution of cell cycle phases and induction of apoptosis was evaluated using flow cytometry with propidium iodide and annexin V-FITC staining. Results. 1,2,4-triazole-3-carboxamides inhibited the proliferation and induced cell cycle arrest of ovarian cancer cells in vitro. Conclusion. these results provide the rationale for further studies of 1,2,4-triazole-3-carboxamides as anticancer drugs.

Objectives. A key step in the synthesis of natural nucleoside analogs is the formation of a glycosidic bond between the carbohydrate fragment and the heterocyclic base. Glycosylation methods differ in terms of regio- and stereoselectivity. A promising method for the highly specific synthesis of new pharmacologically active compounds involves an enzymatic reaction catalyzed by genetically engineered nucleoside phosphorylases. This study is devoted to the synthesis of a library of analogs of nucleoside heterocyclic bases—5-oxymethyl-1,2,4-triazole- 3-carboxamides—in order to investigate the substrate specificity of genetically engineered nucleoside phosphorylases.Methods. A method of cyclization of acylamidrazones obtained from the single synthetic precursor β-N-tert-butyloxycarbonyl-oxalamidrazone was used to parallel-synthesize new 5-alkoxy/ aryloxymethyl-1,2,4-triazole-3-carboxamides. Silica gel column chromatography was used to isolate and purify the synthesized compounds. A complex of physicochemical analysis methods (nuclear magnetic resonance spectroscopy, chromatography, and mass spectrometry) confirmed the structure of the compounds obtained in the work.Results. 5-alkoxy/aryloxymethyl-1,2,4-triazole-3-carboxamides were obtained to study the substrate specificity of genetically engineered nucleoside phosphorylases. The possibility of obtaining new nucleoside analogs by the chemico-enzymatic method was demonstrated on the basis of preliminary assessment results.Conclusions. The physicochemical characteristics of a series of novel 5-alkoxy/aryloxymethyl- 1,2,4-triazole-3-carboxamides were studied along with their potential to act as substrates for the transglycosylation reaction catalyzed by nucleoside phosphorylases.

Low-molecular-weight heparin was synthesized by depolymerization of high-molecular-weight heparin with nitrous acid. Preparative chromatography was used to isolate low-molecular-weight heparins with narrow molecular-weight distributions, as confirmed by size-exclusion HPLC. The average molecular weight of the products according to capillary viscometry decreased with synthesis time (4 h) from 14.0 to 3.4 kDa. Fractions with molecular-weight characteristics, ratios of sulfo- to carboxyl groups, and specific activities corresponding to those of low-molecular-weight heparin isolated from commercially available Fragmin ® were isolated among the products. Low-molecular-weight heparins with characteristics analogous to those of Dalteparin and Nadroparin substances could be obtained depending on the treatment time of high-molecular- weight heparin with nitrous acid in acidic medium.

A new UV-spectrophotometric method for determining the concentration of benzyl fragments in heparin benzyl esters is proposed. The method was validated for linearity, accuracy, and precision in terms of repeatability and intralaboratory reproducibility. The method is intended to characterize heparin benzyl esters, which are intermediates in the synthesis of low-molecular-weight heparin via hydrolytic depolymerization of high-molecular-weight heparin.

The esterification stage of low-molecular-mass heparin (enoxaparin) production by hydrolytic depolymerization of unfractionated heparin was studied and consisted of treating previously synthesized benzethonium heparinate with benzyl chloride. The content of benzyl moieties in the synthesized heparin benzylates and their degree of benzylation were determined using HPLC, PMR, and 13C NMR methods. A carboxylic-acid content of 0.13 ± 0.01 mol/g in the starting heparin was calculated from these results. A new method for estimating the degree of heparin benzylation from PMR and HPLC data was proposed. The benzyl content in the heparin benzylates increased with increasing molar excess of benzyl chloride.