Leukemia, as a part of hemoblastosises, is a malignant blood system disease, which is characterized by bone marrow damage, caused by leukemic stem cells, which appear due to disruption of self-renewal and differentiation of hempoetic stem cells and predecessor cells. In their turn, hemoblastoses are divided into two groups: bone marrow (acute leukemia, chronical leukemia, paraproteinemic hemoblastoses) and outside bone marrow (lymphogranulomatosis, or Hodgkin lymphoma, and non-Hodgkin malignant mymphomas). Nowadays in Ukraine, different kinds of leukemia are cured by various drugs, which have many side effects. Increase in effectivity of chemotherapy of tumor disease is primarily related to creation of new antitumor drugs of selective action. Which is why search for biologically active compounds with antitumor activity is a perspective direction in creation of new drugs. Aim of this work was synthesis of compounds with potential antitumor properties in a variety of [4-(41-chlorophenyl)-5,6,7,8-tetrahydro-2,2a,8a-triazacyclopenta[c,d]-azulen-1-yl-methyl]-para-tolylamin derivatives. As the objects of our studies, we have picked the derivatives of [4-(41-chlorophenyl)-5,6,7,8-tetrahydro-2,2а,8а-triazacyclopenta[c,d]-azulen-1-yl-methyl]-para-tolilamin (8 and 10 a, b). [4-(41-Chlorphenyl)-5,6,7,8-tetrahydro-2,2а,8а-triazacyclopenta[c,d]azulen-1-yl-methyl]-para-tolylamin (8) was obtained by boiling of equimolar quantities of 3-(41-methylphenyl)aminomethyl-6,7,8,9-tetrahydro-5Н-[1,2,4]triazolo[4,3-a]azepin (5) and α-brom-4-chloracetophenon in ethylacetate. Thioamides (10 a, b) were obtained by interaction of amin (8) with corresponding arylisothiocyanates (9 а, b) in dry benzene. Antitumor activity of [4-(41-chlorphenyl)-5,6,7,8-tetrahydro-2,2а,8а-triazacyclopenta[c,d]azulen-1-yl-methyl]-para-tolylamin (8) was studied in National Cancer Institute of Health, USA within Development Therapeutic Program. In experimental conditions [4-(41-chlorphenyl)-5,6,7,8-tetrahydro-2,2а,8а-triazacyclopenta[c,d]azulen-1-yl-methyl]-para-tolylamin (8) showed ability to inhibit growth of cancerous leukemia cells of CCRF-CEM, HL-60(TB), K-562, MOLT-4, RPMI-8226 and SR lines, higher than standard – 5-fluorouracil. Towards HL-60(TB) cells [4-(41-chlorphenyl)-5,6,7,8-tetrahydro-2,2а,8а- triazacyclopenta[c,d]azulen-1-yl-methyl]-para-tolylamin exceeds standard in effectivity by 64.68%. For K-562, MOLT-4, RPMI-8226 and SR cells, those numbers are equal to: 85.88%, 84.95%, 42.10% and 36.82% correspondingly. Towards CCRF-CEM cells, this compound not only inhibits cell growth and division, but also destroys them by 20.34%. Thus conducted studies confirm perceptivity of search for compounds with antitumor action on the basis of [4-(41-chlorophenyl)-5,6,7,8-tetrahydro-2,2а,8а-triazacyclopenta[c,d]azulen-1-yl­methyl]-para-tolylamin.

Nowadays, control of viral diseases becomes especially relevant, considering spreading of influenza A (subtype H1N1) in this season and appearance of new coronavirus SARS-CoV-2, which caused their epidemic spreading in the world. This is why development and introduction of new highly effective antiviral drugs are a relevant direction of pharmaceutical chemistry. The aim of research is to synthesize the derivatives of (4,6-bis-amino[1,3,5]triazin-2-yl-sulphanyl)-Naryl-acetamide and to study the antiviral activity for FluA (H1N1) virus California/07/2009 at primary pharmacological screening stage. The investigated compounds – (4,6-bis-amino[1,3,5]triazin-2-yl-sulphanyl)-N-aryl-acetamide derivatives, were synthesized on the basis of 4,6-bis-ethylamino[1, 3,5]triazin-2-tiol. The antiviral activity of (4,6-bis-amino[1,3,5]triazin-2-yl-sulphanyl)-N-(2,4,6-trichlorphenyl)-acetamide against the virus FluA (H1N1) California/07/2009 was evaluated on MDCK cell culture test in vitro. It has been shown that the test substance exhibits high antiviral activity against the influenza A virus H1N1 California/ 07/2009 with effective concentration of EC50 0,6 μg/ml and the selectivity index SI > 170 (for Ribavirin SI > 160 and Amizona SI > 2,1). The data obtained substantiate the expediency of further study of derivatives of (4,6-diamino[1,3,5] triazine-2-yl-sulphanyl)-N-aryl-acetamide as potential antiviral agents.

Aim. To synthesize 2-(4,6-di(pyrrolidin-1-yl)-1,3,5-triazin-2-yl)-N-(alkyl, aryl)hydrazine-1-carbothioamides and study their antiviral activity against yellow fever virus (YFV). Results and discussion. The target 2-(4,6-di(pyrrolidin-1-yl)-1,3,5-triazin-2-yl)-N-(alkyl, aryl)hydrazine-1-carbothioamides were obtained in three-step format from cyanuric chloride in good to high yields. The carbothioamides synthesized were estimated to possess the antiviral activity against YFV. The results obtained indicate that most of the compounds studied show the inhibitory activity against YFV in concentrations ≤10 μg/mL. For the most active substances, EC90 was in the range of 0.06 – 2.2 μg/mL. Good effective concentration values were accompanied by low levels of cytotoxicity resulting in excellent selectivity index values. The data obtained also indicate that the presence of an alkyl substituent in ortho-position of the N-aryl fragment is crucial for an effective inhibition of YFV growth. Experimental part. 2-(4,6-Di(pyrrolidin-1-yl)-1,3,5-triazin-2-yl)-N-(alkyl, aryl)hydrazine-1-carbothioamides were synthesized starting from cyanuric chloride in three steps by its successive interaction with two equivalents of pyrrolidine, hydrazine and a series of alkyl-/arylisothiocyanates. The antiviral and cytotoxic activities of the target carbothioamides were studied in the Southern Research Institute (SRI, Birmingham, Alabama) by the viral cytopathic effect reduction assay and the virus yield reduction assay. Conclusions. 2-(4,6-Di(pyrrolidin-1-yl)-1,3,5-triazin-2-yl)-N-(alkyl, aryl)hydrazine-1-carbothioamides synthesized have been proven to be a promising class of compounds for treating such a severe viral disease as yellow fever.

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В даній статті досліджуються питання щодо сутності публічного обвинувачення, як основної кримінально-процесуальної функції прокурора. Аналізуються точки зору вчених, щодо моменту виникнення обвинувальної функції у кримінальному процесі та її змісту. Наводяться аргументи відносно того, що підтримання публічного обвинувачення - це го­ловна і єдина кримінально-процесуальна функція прокурора при розгляді матеріалів кримі­нального провадження судом першої інстанції, яка займає домінуюче становище у системі кримінально-процесуальних функцій. Зазначається, що виконання прокурором у суді про­цесуальної функції обвинувачення - це практична реалізація тих висновків, до яких він прийшов на стадії досудового розслідування. Функція обвинувачення, що виконується про­курором у кримінальному судочинстві, спрямована не тільки на висунення обвинувачення і доведення його перед судом, а виступає також правовим засобом захисту інтересів особи, держави і суспільства від злочинних посягань в цілому.