Sergey V. Sysolyatin

Synthesis of 4-(N-Benzoylaminoacetyl)-2,6,8,12-tetraacetyl-2,4,6,8,10,12-hexaazaisowurtzitane | Balakhnina | Proceedings of Universities. Applied Chemistry and Biotechnology Синтез 4-(N-бензоиламиноацетил)-2,6,8,12-тетраацетил-2,4,6,8,10,12-гексаазаизовюрцитана | Балахнина | Известия вузов. Прикладная химия и биотехнология

Objective. To study anticonvulsant activity of thiowurtzine in seizure models induced by pentylenetetrazol and thiosemicarbazide. Material and methods. Experiments were conducted on male CD-1 mice. Thiowurtzine was administered intragastrically at doses of 50, 100 and 200 mg/kg. Carbamazepine (100 mg/kg) was used as a reference drug. Anticonvulsant activity was investigated in antagonism tests with pentylenetetrazol (PTZ 140 mg/kg subcutaneously) and thiosemicarbazide (TSC 30 mg/kg subcutaneously). Anticonvulsant activity was assessed considering latency of various seizure stages, their frequency, and animal survival. Results. In PTZ test, thiowurtzine 100 mg/kg significantly prolonged latent period of myoclonic seizures by 92% and clonic seizures by 95%, as well as survival time by 73% compared to the control group. All changes were significant. Survival reached 41.7% that was comparable to the effect of carbamazepine. At 200 mg/kg, efficacy decreased that indicated a narrow therapeutic window. In TSC model, thiowurtzine did not significantly affect survival. However, dose 100 mg/kg reduced the number of the most severe tonic seizures by 31%. Conclusion. Thiowurtzine possesses anticonvulsant activity, most pronounced in GABA-dependent pentylenetetrazol model. These data indicate membrane-stabilizing effect and expand potentials for this compound in comorbid conditions.

Benzimidazoles represent a key class of heterocyclic compounds that stand out for their wide range of biological activity. This scaffold has become particularly important in medicinal chemistry due to its ability to mimic the purine bases of natural nucleosides, which ensures active interaction with biological targets. Today, the benzimidazole moiety provides a basis for many clinically significant drugs, such as omeprazole, albendazole, pantoprazole, and others. The potential of benzimidazole derivatives as inhibitors of cancer cell proliferation has actively been studied in recent years. In this regard, the development of highly selective, low-toxicity cytostatic molecules based on benzimidazole is highly relevant for modern oncopharmacology. This paper provides a systematic overview of advances reported over 2023–2026 in the anticancer activity of benzimidazole derivatives. The focus is on the results of preclinical studies on a panel of cell lines, including cervical carcinoma (HeLa), bladder carcinoma (HTB-9), non-small cell lung cancer (A-549), colorectal carcinoma (HCT-116), colon cancer (HT-29), chronic myeloid leukemia (K-562), acute lymphoblastic leukemia (CCRF-CEM), breast adenocarcinoma (MCF-7), triple-negative breast cancer (MDA-MB-231), hepatocellular carcinoma (HepG2), and glioblastoma (LN-18). The data analysis revealed the most promising compounds that exhibit a pronounced cytostatic activity against cancer cells. The relationship between the molecular structure and activity of the examined compounds was evaluated. This review summarizes the latest achievements in this field and can serve as a basis for a further search for novel benzimidazole skeleton-containing anticancer agents.

Despite the wide range of drugs, the problems of insufficient efficiency and side effects remain relevant, which stimulates active searches for new biologically active compounds with improved therapeutic properties. In this regard, derivatives of 1,2,3-triazoles-heterocyclic structures are of great interest, possessing great potential for the development of new effective pharmaceuticals, due to their wide range of biological activity, including antimicrobial, antitumor, antiviral. This necessitates the study of their properties, the search for ways to synthesize new molecules and the methods for obtaining already known compounds optimization. In this work, the synthesis of new 5-amino-1,2,3-triazoles derivatives by the cyanoacetic ester with 2-(azidomethyl)-1H-benzoimidazole and 2-azidoacetamide reaction is presented. Optimization of cycloaddition conditions in the systems: DMSO/potassium carbonate, DMSO/sodium methylate and methanol/sodium methylate was carried out. The key role of the solvent and base on the reaction efficiency is shown, which ensures the target product maximum yield. Products highest yield was achieved in the methanol/sodium methylate system. Hydrolysis of synthesized 1,2,3-triazoles esters leads to carboxylic and dicarboxylic acids, which have not been previously described in the literature. All new compounds obtained in the work were confirmed with IR and 1H, 13C NMR spectroscopy. All the new compounds obtained in the work have a high predictive exhibiting antitumor activity probability, according to the computer analysis results in the PASSonline program. The results on the 5-amino-1,2,3-triazole-4-carboxylates and their carboxylic acids synthesis studies make it possible to expand the potential substances range for the oncological diseases treatment and contribute to the 5-amino-1,2,3-triazoles chemistry development. For citation: Strokova S.V., Lenskiy M.A., Vilisova D.N., Sysolyatin S.V., Gultikova M.V. Synthesis and study of new 5-amino-1,2,3-triazoles as potential antitumor agents. ChemChemTech [Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.]. 2026. V. 69. N 3. P. 96-104. DOI: 10.6060/ivkkt.20266903.7257.

Objective. To assess analgesic action of the newly patented compound from the class of hexaazaisowurzitanes as compared to tramadol in a battery of behavioral tests with various nociceptive systems. Material and methods. The experiments were performed in male mice of CD1 stock. A newly patented 4-(2-ethoxyacetyl)-2.6,8.10.12-pentaacetyl2.4,6.8,10.12hexaazatetracyclo [5.5,0.03.11.05.9]dodecane (M1) was administered daily through a probe at a dose 25—200 mg/kg. Tramadol was administered in a single dose 10 mg /kg for 1-3 days. The last injection was an hour before experimental manipulations. Analgesic effect was evaluated in a three-day administration on a model of chemical irritation of the peritoneum, in a single administration (test of central pain genesis “hot plate”) and mechanical paw compression (Randall-Selitto method). Results. Analysis of specific pharmacological activity in models of somatogenic pain (thermal, visceral pain, mechanical compression) revealed high analgesic activity of the newly synthesized compound 4-(2-ethoxyacetyl)-2.6,8.10.12-pentaacetyl 2.4,6.8,10.12 hexaazatetracyclo[5.5,0.03.11.05.9]dodecane (substance M1). The last one is comparable or exceeds the effect of tramadol. Analgesic effect of the new compound is realized at different levels of conduction and modulation of pain sensitivity. Conclusion. The results of experimental tests with different nociception systems indicate advisability of further preclinical studies of the newly synthesized molecule with high analgesic therapeutic potential.

Aim. To assess the anti-inflammatory and gastroprotective effects of ethowurtzine compared to the reference drug diclofenac in a rat model of chronic inflammation; to evaluate the influence of ethowurtzine on nitric oxide production as a possible mechanism of its anti-inflammatory effects.Materials and methods. The object of the study was a new patented ethowurtzine from the class of hexaazaizowurtzitane derivatives with an acceptable safety profile.The gastroprotective and anti-inflammatory effects of ethowurtzine compared to diclofenac were studied in a model of chronic inflammation using 69 female SD rats. The compound (12.5–100 mg / kg) and a non-selective COX inhibitor diclofenac (5 mg / kg) were administered intragastrically for 7 days, 1 hour before subcutaneous implantation of a cotton swab. On day 8, the proliferative response (%), the exudative response (%), and the ulcerogenic effect of the compounds were assessed.Nitric oxide (NO) synthesis by macrophages obtained from peritoneal cavity of 25 C57Bl/6 mice (in vitro inflammation model) was evaluated by the concentration of nitrites in the cell supernatant after incubating cells in the presence of ethowurtzine and / or lipopolysaccharide (LPS) for 48 hours. The classical MTT test (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT, Sigma, USA)) was used to assess the effects of ethowurtzine on macrophage proliferation.Results. A comparative study of ethowurtzine and diclofenac in a rat model of chronic inflammation revealed the predominant anti-exudative effect of the new substance and a suppressive effect on granulation tissue proliferation comparable to that of NSAID.The macroscopic examination of the gastric mucosa in rats receiving ethowurtzine did not reveal any ulcer damage. On the contrary, in 30% of the rats receiving diclofenac, the severity score of ulcer was 2. In the in vitro inflammation model, the addition of LPS to the macrophage culture resulted in a significant increase in NO synthesis. The introduction of ethowurtzine at different concentrations together with LPS dose-dependently reduced the NO production. A statistically significant decrease in the NO synthesis was noted at high doses of the test substance compared to the group of isolated LPS use. However, the introduction of ethowurtzine at different concentrations together with LPS did not cause statistically significant changes in the proliferation of macrophages compared to the group with the isolated LPS use.Conclusion. The newly synthesized ethowurtzine had a pronounced anti-inflammatory effect and caused a significant decrease in granulomatous infiltration and exudative edema in the chronic inflammation model. Suppression of the NO synthesis is one of the possible mechanisms in the anti-inflammatory effect of ethowurtzine. The obtained data allow to suggest possible administration of the new patented analgetic ethowurtzine in chronic pain treatment associated with inflammation.

Protective groups are of great importance when choosing a strategy for the synthesis of organic substances. The multi-stage nature of syntheses of target organic molecules, various conditions, lability and reactivity of substrates, intermediate and target products, and individual functional groups of molecules force chemists to use a variety of protective groups to prevent decomposition of the desired substances, increase the regioselectivity of the synthesis processes, and eliminate the influence of aggressive reagents on labile reactive centers in the molecule. Along with this, the process of removing protective groups involves selecting conditions that reduce or eliminate undesirable side reactions. Among these methods is hydrogenation, one of the special cases of which is reductive debenzylation. This reaction of introducing and removing a benzyl group is one of the most common reactions in organic synthesis, since the relative ease of introduction and the chemical and thermal stability of the benzyl group and the possibility of its indirect introduction are the preferred factors for using this method by synthetic chemists. This reaction is used for the synthesis of a wide range of compounds, such as drugs, high-energy substances, and polymers [1–11]. Since the reaction is universal, many organic molecules can act as a substrate for this process. Removal of the benzyl group involves the use of various methods, depending primarily on the structure and properties of the original substrates. This review considers the methods of reductive and oxidative N- and O-debenzylation using catalysts of various types and addresses approaches to the removal of benzyl protection in different classes of organic substances, such as aromatic compounds, crown ethers, tetrazoles, triazoles, substituted hexoses, and isowurtzitanes.