Introduction . In recent years, the creation and use of drugs for antitumor therapy, which have improved the quality of life and survival of cancer patients, has become a crucial event in the development of oncology. It is known that urea derivatives are included in the class of drugs with anti-angiogenic properties. The addition of a carbohydrate residue to urea derivatives helps to improve the solubility, targeted drug deliveiy in the body (targeting), and the elimination of side effects. In order to search for new compounds with anti-angiogenic properties, we have synthesized a number of compounds, some of which are previously unknown urea derivatives. Purpose of the study — synthesis of urea derivatives based on sugary nitrosocarbamidetransamidation. To evaluate using in silico and in vitro methods, there is the ability to create new anticancer drugs based on new glycosidic urea derivatives. Materials and methods . Pre-experimental prediction of biological activity was performed using a computer system PASS. Cytotoxic activity was determined by the MTT method. For the MTT assay, cells were dropped into 198 µl of RPMI-1640 complete medium in 96-well plates. After one day, the test compounds were added to each well in concentration 100 µmol. After 72 hours, 20 µl of MTT solution was added to each well. The intensity of the medium staining was measured on a Multiskan EX photometric immunoassay analyzer at λ = 540 nm. Results . From the number of virtual compounds studied, for 5 compounds a high probability of antineoplastic activity and a low probability of cytotoxic activity in silico are predicted. Compounds were synthesized: N-(β-D-galactopyranosylcarbamoyl-l)-2-isonicotin-semicarbazide, l-[(N- β -D-galactopyranosyl)-carbamoyl]-3,5-dimethylpyrazoIe, N-( β -D -galactopyranosylcarbamoyl)-p-bromophenylurea, N-( β -D -galactopyranosyl)-p-chlorophenylurea, N-( β -D -glucopyranosyl)-p-chlorophenylurea. The compounds did not show cytotoxic activity in vitro. Conclusion . For the studied compounds, a tow probability of cytostatic activity manifestation (as confirmed experimentally) and a high probability of antitumor activity manifestation are virtually predicted.

New propargylamines were synthesized in 72–75% yields by the interaction of 19-alkynylbetulin and 28-O-propargyl glycinamide of oleanolic acid with N-methylpiperazine under the Mannich reaction conditions. 19-[1-Methyl-4-prop-2-yn-1-yl-piperazine]-20,29,30-trinorbetulin was shown to manifest anticancer activity against one line of leukemia cells and two lines of colon cancer cells, whereas the growth of leukemia cells SR in the presence of 4-(4-methylpiperazin-1-yl)but-2-yn-1-yl-N-(3-hydroxy-28-oxoolean-12-en-28-yl)glycinate was 8%.

2,3-Indolotriterpenic alcohols have been synthesized for the first time by successive modification of 3-oxo triterpenic acids (Fisher reaction, reduction of С17-СOOH, cyanoethylation) and characterized by physicochemical methods of analysis. It has been found that 2,3-indolouvaol and 2,3-indolo-28-cyanoethoxybetulin exhibit antitumor activity in vitro toward NCI-H522 lung cancer (–12.65%) and COLO 205 colon cancer cells (–42.78%), respectively. The activity of 2,3-indolooleanolic and 2,3-indolobetulinic acids toward 19 and 9 cell lines of six and four human cancers, respectively, has been revealed. Indole-fused triterpenoids have been shown to hold promise as objects in the search for novel antitumor agents.

Objective: to study the cytotoxic activity of the zinc (II) and cadmium (II) iodide complexes with antipyrine (AP), caffeine (caf) and 1,10-phenantroline (phen) in comparison with that of free ligands, zinc (II) and cadmium (II) iodides in vitro. Materials and methods. The cytotoxic activity of the zinc (II) and cadmium (II) iodide complexes with AP, caf and phen in comparison with that of free ligands, zinc (II) and cadmium (II) iodides was investigated by methylthiazole tetrazolium assay using 5 human tumor cell lines. Results. It has been found that all 3 cadmium complexes demonstrate cytotoxic activity towards all 5 cell lines with concentration of inhibition of 50 % cell growth 5.5-84.0 mkM. Cytotoxicity of the most active diiodo(1,10-phenantroline)cadmium was slightly above than that of the respective ligand. One zinc-containing complex (diiodo(1,10-phenantroline)zinc) demonstrated significant activity towards 3 cell lines. The Jurkat cells were the most sensitive to studied compounds. Conclusion. It seems that zinc (II) and cadmium (II) iodide complexes with organic ligands are promising ones as potential antitumor drugs for further investigations both in vitro and in vivo.

Objective: to evaluate the prospects of the glycosides of indolocarbazole containing amino acid residues as potential antitumor compounds. Materials and methods. For 32 compounds by structural formulas using the methods of chemoinformatics, a number of molecular descriptors and the probability of manifestation of various types of biological activity were calculated, the cytotoxic activity was evaluated in vitro by methylthiazole tetrazolium (MTT) assay using five human tumor cell lines. Results. For the studied amino acid derivatives of glycosides of indolocarbazole, a high probability of antitumor activity with a low probability of cytotoxic activity in vitro is predicted by computer method. Low cytotoxic activity was confirmed in the MTT test on 5 cell lines. Computer methods were used to predict the mechanisms of possible antitumor activity and to calculate a number of molecular descriptors that are important for the qualification of substances as potential drugs. Conclusion. It is expedient to study the antitumor activity of amino-acid derivatives of glycosides of indolocarbazole in experiments on animals with transplanted tumors.

Objective: to study the cytotoxic activity of the zinc (II) and cadmium (II) iodide complexes with antipyrine (AP), caffeine (caf) and 1,10-phenantroline (phen) in comparison with that of free ligands, zinc (II) and cadmium (II) iodides in vitro. Materials and methods. The cytotoxic activity of the zinc (II) and cadmium (II) iodide complexes with AP, caf and phen in comparison with that of free ligands, zinc (II) and cadmium (II) iodides was investigated by methylthiazole tetrazolium assay using 5 human tumor cell lines. Results. It has been found that all 3 cadmium complexes demonstrate cytotoxic activity towards all 5 cell lines with concentration of inhibition of 50 % cell growth 5.5-84.0 mkM. Cytotoxicity of the most active diiodo(1,10-phenantroline)cadmium was slightly above than that of the respective ligand. One zinc-containing complex (diiodo(1,10-phenantroline)zinc) demonstrated significant activity towards 3 cell lines. The Jurkat cells were the most sensitive to studied compounds. Conclusion. It seems that zinc (II) and cadmium (II) iodide complexes with organic ligands are promising ones as potential antitumor drugs for further investigations both in vitro and in vivo.

The aim of this study was to examine the anticancer activity of rare earth elements complexes with antipirin. Materials and methods. We have studied the cytotixic activity of in vitro and antineoplastic activity in vivo of 28 iodides and perchlorates containing as a ligand antipirine. Results. Here we show, that non of tested compounds exert cytotoxic action on 5 human cancer cell lines of different histogenesis at a concentration of 100 ßM. However, we observe that two complexes of antipirine derivatives with iodides of gadolinium and neodymium possess anti-tumor activity in experiments with transplantable solid tumors. Conclusion. The data obtained indicate the feasibility of further studies of these two complexes on a larger number of mice, with changing doses and routes of administration. We also suggest the investigation of these compounds on ascites tumors.

Осуществлен синтез лупановых С-28-имидазолидов, содержащих 3-оксо-, 3-гидроксиимино- и 2-циано-2,3-секо-4(23)-ен фрагменты в цикле А. При испытаниях in vitro наибольшую противоопухолевую активность показал 3-оксимино-луп-20(29)-ен-28-ил-1Н-имидазол-1-карбоксилат, значительно ингибируя рост или индуцируя гибель клеток рака легкого, толстой кишки, молочной железы, центральной нервной системы, яичника, простаты, почки, лейкозов и меланомы. В исследованиях на мышах наблюдали его умеренное противоопухолевое действие на перевиваемые аденокарциному молочной железы Ca755 и аденокарциному толстого кишечника AКАТОЛ.

Lupane C-28-imidazolides containing 3-oxo-, 3-hydroxyimino-, and 2-cyano-2,3-seco-4(23)-ene fragments in cycle A have been synthesized. 3-3-Hydroxyimino-lup-20(29)-en-28-yl-1H-imidazole-1-carboxylate showed the highest antineoplastic activity in experiments in vitro, significantly inhibiting the growth and inducing the death of cells of lung, colon cancer, breast, central nervous system, ovarian, prostate, renal, leukemia, and melanoma cancers. In experiments on mice, it had a moderate antineoplastic effect on inoculated breast adenocarcinoma Ca755 and large intestine adenocarcinoma AKATOL.

Synthesis of lupane C28-imidazolides, contained 3-oxo-, 3-oximino- and 2-cyano-2,3-seco-4(23)-en-frag ments in cycle A was carried out. The most antitumor activity at. in vitro testing showed 3-oximino-lup- 20(29)-en-28-yl-1H-imidazole-1-carboxylate; which inhibited the growth or induced apoptosis of non-small lung cancer, colon cancer, breast cancer, CNS cancer, ovarian cancer, prostate cancer, leucosis, melanoma cells. In experiments in mice its moderate antitumor activity against grafted breast adenocarcinoma Ca 755 and adenocarcinima of colon was observed.

Осуществлен синтез и скрининг противоопухолевой активности in vitro (цитотоксичности) разнообразных кислород-, азот-, серо- и платиносодержащих производных аллобетулина, в том числе – с различным расположением двойных связей в кольцах А и В, пента- и гексациклическим кольцом А, 21-ацетил-20,28-эпокси-18 19 -урсано-изомерным циклом Е. Значимую цитотоксическую активность проявили (3R,5R)-19 28-эпокси-4,5-секо-18 -олеан-3(5)-озонид в культуре клеток меланомы MeWo и 2,3-индоло-21 -ацетил-20 28-эпокси-18 19 -урсан в культуре клеток лейкоза SR. 3S,5S-Диастереоизомер первого из них цитотоксичности не проявил.

Antineoplastic activity of Stellanin ® as drug “drops for per os intake”, its active substance 1,3-diethylbenzimidazolium triiodide and its methabolite 1,3-diethylbenzimidazolium monoiodide was studied on mouse transplantable tumors: lymphocytic leukemia P388, melanoma B16 and colon cancer AKATOL. Substances 1,3-diethylbenzimidazolium triiodide and its methabolite 1,3-diethylbenzimidazolium monoiodide didn’t reveal antineoplastic effect on mouse leukemia P388. Stellanin ® both as drug and as substance administered per os to mice with melanoma B16 and colon cancer AKATOL showed dose-dependent stable antitumor effect (70-50% tumor growth inhibition) during 2 weeks after treatment completion. The optimal schedules of Stellanin ® treatment were determined: single dose of 15-30 mg/kg 2-3 times a day during 10 days or dose of 10 mg/kg one time a day during 20 days. 1,3-diethylbenzimidazolium monoiodide with explored dose range didn’t show any antineoplastic activity.

A variety of oxygen-, nitrogen-, sulfur-, and platinum-containing allobetulin derivatives, including those with different positions of double bonds in rings A and B, the penta- and hexacyclic ring A, and the 21-acetyl-20,28-epoxy-18α,19βH-ursanoisomeric cycle E, have been synthesized, and the screening of their antineoplastic activity in vitro (cytotoxicity) has been carried out. A significant cytotoxic activity was exhibited by (3 R ,5 R )-19β,28-epoxy-4,5-seco-18α-olean-3(5)-ozonide toward MeWo melanoma cells and by 2,3-indolo-21β-acetyl-20β,28-epoxy-18α,19βH-ursane toward SR leukosis cells. The 3 S ,5 S -diastereoisomer of the former compound showed no cytotoxicity.

На основе бетулоновой и олеаноновой кислот осуществлен синтез 3-дезокси-3а-гомо-3а-аза-производных бетулина и эритродиола. Наибольшую противоопухолевую активность in vitro широкого спектра действия показал 3-дезокси-3а-гомо-3а-аза-28-гидрокси-12(13)-олеанен, который по результатам углубленного изучения in vitro можно рекомендовать для испытаний in vivo. Его модификация по положению С28 введением метоксициннамоильного фрагмента привела к потере противоопухолевой активности. 3-Дезокси-3а-гомо-3а-аза-производные бетулина (3-(аминопропил)-, 28-(2-карбоксиэтил)карбокси- и 28-циннамоилокси-) в целом проявили умеренную противоопухолевую активность в отношении клеток рака толстой кишки, молочной железы и лейкоза.

3-Deoxy-3 a -homo-3 a -aza derivatives of betulin and erythrodiol have been synthesized from betulonic and oleanonic acids. 3-Deoxy-3 a -homo-3 a -aza-28-hydroxy-12(13)-oleanene showed the highest antineoplastic activity of the broad spectrum in vitro; the results of an extensive examination of the derivative in vitro enable one to recommend it for in vivo tests. The modification of the compound in the position C28 by the introduction of a methoxycinnamoyl fragment led to the loss of the antineoplastic activity. As a whole, 3-deoxy-3 a -homo-3 a -aza derivatives of betulin [3-(aminopropyl)-, 28-(2-carboxyethyl)carboxy-, and 28-cinamoyloxy-] exhibited a moderate antineoplastic activity toward large intestine cancer, breast cancer, and leukemia cells.

The synthesis of (7 R ,8 S )-epoxy-(13 R ,17 R )-trioxolane abietic acid was carried out and its structure was established by X-ray diffraction. The antineoplastic activity and the ability to induce apoptosis that were predicted by a PASS computer system, correlate well with the experimentally found cytotoxic activity towards the MeWo malignant cell line. The results of tests on animals showed that abietic acid and its (7 R ,8 S )-epoxy-(13 R ,17 R )-trioxolane derivative have anti-inflammatory and antiulcer activities in the absence of side effects.