Yu. V. Ostapiuk’s research while affiliated with Lviv University and other places

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Publications (24)


Effect of a thiazole derivative on the activity of antioxidant enzymes in murine lymphoma cells
  • Article

November 2024

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1 Read

Visnyk of Lviv University Biological series

Ya. Shalai

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V. Koberenko

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M. Ilkiv

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[...]

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A. Babsky

Previous in vitro studies have demonstrated a pronounced cytotoxic effect of the thiazole derivative N-(5-Benzyl-13-thiazole-2-yl)-35-dimethyl-1-benzofuran-2-carboxami­de (BF1) on tumor cells. Additionally, it has been determined that scavengers of reactive Oxygen species (ROS) significantly reduce the cytotoxic effect of BF1. In this study, the influence of BF1 on the activity of superoxide dismutase (SOD) and catalase (CAT), both normally and in the presence of ascorbic acid, in mouse Nemeth-Kellner lymphoma (NK/Ly) cells has been studied to evaluate the possible role of antioxidant activity during the action of this substance. The experiments were performed using nonlinear male mice weighing 20–30 g. Intraperitoneal inoculation of 10–15 million cancer cells into the mice induced the ascites form of lymphoma. The thiazole derivative (BF1) was dissolved in dimethyl sulfoxide and added to the test samples at 1, 10, and 50 μM final concentrations. Superoxide dismutase (SOD) and catalase (CAT) activities were determined spectrophotometrically in a homogenate of the lymphoma cells after incubation with the drug for 30 minutes. The baseline level of SOD in the lymphoma of the mice was 0.33±0.02 activity units/min×mg protein. BF1 significantly increased the enzyme activity by 35 % and 29 % at concentrations of 10 (p<0.01) and 50 μM (p<0.05), respectively. The baseline level of CAT activity was 4.61±0.17 nmoles H2O2/min×mg protein, and this significantly decreased by 15 % (p<0.05) and 20 % (p<0.01) following the action of the thiazole derivative at a concentration of 10 and 20 μM, respectively. The increase of SOD activity, coupled with a decrease or absence of changes in CAT activity, may be cytotoxic to cancer cells. Simultaneously, upon the addition of ascorbic acid as a scavenger of ROS to the environment, the activities of SOD and CAT did not change under the action of BF1 at any of the investigated concentrations. Therefore, the effect of the thiazole derivative BF1 has been canceled in the presence of ROS scavengers in the environment. This may indicate the dependence of the cytotoxic effect of BF1 on the presence of ROS in tumor cells.


Synthesis of 4-amino-1-arylpyrazoles based on ethyl 2 cyano 2-(2-arylhydraziniidene)acetates

October 2024

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5 Reads

Visnyk of the Lviv University Series Chemistry

Описано метод отримання низки нових 3,5-дизаміщених 4-аміно-1‑арилпіразолів. Показано, що взаємодія етил 2-ціано-2-(2-арилгідразиніліден) ацетатів з галогенокетонами відбувається за наявності основи в умовах реакції Дікмана-Торпа. Етил 2-ціано-2-(2-арилгідразиніліден)ацетати одержано реакцією азосполучення під час взаємодії арилдіазонієвих солей з етил 2‑ціаноацетатом. Ключові слова : 4-амінопіразоли, арендіазонію хлориди, реакція азосполучення, реакція Торпа-Циглера.


Activity of antioxidant enzymes in hepatocytes of mice with lymphoma under the action of thiazole derivative in complex with polymeric nanocarrier

October 2023

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12 Reads

The Animal Biology

Many chemotherapeutics drugs have low water solubility, which potentially can decrease their anticancer potential. The use of drug delivery systems has proven to be highly effective in addressing the challenges associated with delivering hydrophobic chemotherapy drugs to tumor tissues. However, two major issues that arise in the clinical nanoparticle-based treatment of cancer are hepatotoxicity and suppression of the hematopoietic system, which can limit their medical applicability. As previously established, thiazole derivative N-(5-benzyl-1,3-thiazol-2-yl)-3,5-dimethyl-1-benzofuran-2-carboxamide in complex with polymeric nanocarriers (nanomicelles) based on polyethylene glycol exhibited a greater level of cytotoxicity towards specific tumor cell lines melanoma, glioblastoma, hepatocarcinoma, leukemia, etc. This compound and its complexes with polymeric nanomicelle significantly changed the activity of antioxidant enzymes in lymphoma cells. Therefore, the purpose of this study was to examine the impact of a thiazole derivative with polymeric nanomicelles based on polyethylene glycol on the hepatocytes (liver cells) of mice that had been implanted with Nemet-Kelner lymphoma. The investigated compounds thiazole derivative, polymeric nanomicelle, and combination of thiazole derivative with nanomicelle at a final concentration of 10 μM were added to the liver samples and incubated for 10 min. The activity of antioxidant defense system enzymes such as superoxiddismutase, catalase, glutathionperoxidase was determined in liver homogenate under the action of studied compounds in vitro. It was reported that neither thiazole derivative, nanomicelle, nor their complex changed the activity of antioxidant enzymes in hepatocytes from mice with lymphoma. Thiazole derivative and it complex with nanomicelle had limited negative side effects in the mice with lymphoma. The investigated compounds were not hepatotoxic toward murine liver cells.


Bioenergetic characteristics of the murine Nemeth-Kellner lymphoma cells exposed to thiazole derivative in complex with polymeric nanoparticles
  • Article
  • Full-text available

February 2023

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21 Reads

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1 Citation

The Ukrainian Biochemical Journal

The development of a new anticancer drugs targeted at energy metabolism of tumor cells is a promising­ approach for cancer treatment. The aim of our study was to investigate the action of thiazole derivative N-(5-benzyl-1,3-thiazol-2-yl)-3,5-dimethyl-1-benzofuran-2-carboxamide (BF1) and its complex with PEG based polymeric nanoparticle (PEG-PN) on respiration and mitochondrial membrane potential in murine NK/Ly tumor cells. The rate of oxygen uptake in NK/Ly cells was recorded by a polarographic method using a Clark electrode. The mitochondrial potential relative values were registered using fluorescence TMRM dye. No changes in glucose-fuelled basal respiration or maximal FCCP-stimulated respiration was detected after 15-min incubation of cells with BF1 (10 µM), PEG-PN or BF1 + PEG-PN complex Fluorescent microscopy data showed that BF1 or PEG-PN separately had no effect on the value of mitochondrial membrane potential, while BF1 + PEG-PN complex caused a significant decrease in mitochondrial membrane potential, indicating­ on the decrease of NK/Ly cells viability. Keywords: cell respiration, mitochondrial membrane potential, NK/Ly tumor cells, PEG, polymeric nanoparticles, thiazole derivative

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Fig. 1. Effect of thiazole derivative (BF1), unconjugated PEG-based polymeric nanoparticle (Th1) and complexes of BF1 with PEG-PN (Th2) on the level of hydroperoxides (A) and TBA-positive products (B) in the hepatocytes of tumor-bearing mice. Mean ± SD; n = 5
Safety profile of thiazole derivative and its complex with PEG-based polymeric nanoparticles on liver and blood cells in tumor-bearing mice

January 2022

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5 Reads

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1 Citation

Studia Biologica

Background. Drug delivery systems (DDS) have demonstrated a significant ability to overcome many of the challenges associated with the delivery of hydrophobic chemotherapeutic compounds to tumor tissues. However, hepatotoxicity and suppression of the hematopoietic system are the key problems in the clinical treatment of cancer by nanoparticle-based DDS that can limit their medical exposure. The aim of this work was to investigate the effect of thiazole derivative N-(5-benzyl-1,3-thiazol-2-yl)-3,5-dimethyl-1-benzofuran-2-carboxamide (BF1) conjugated with PEG-based polymeric nanoparticles (PEG-PN – Th1) on the hepatocytes and blood hematological parameters of mice with grafted NK/Ly. Materials and Methods. The experiments were conducted on white wild-type male mice with grafted NK/Ly lymphoma. Investigated compounds BF1, PEG-PN Th1, and combination of PEG-PN + BF1 (Th2) at a final concentration of 10 μM were added to the liver samples and incubated for 10 minutes. The level of lipid peroxidation products and the level of antioxidant defense system (AOS) enzymes were determined according to the techniques described below. The cytological parameters of blood were investigated after the treatment of mice with BF1 in concentrations of 10 and 20 mg/kg, PEG-PN (20 mg/kg) and Th2 complex (10 mg/kg). On the 14th day of the experiment, blood was taken from all groups and the number of erythrocytes, leukocytes and leukocyte formula were counted. Results. It was reported that neither BF1, PEG-PN, nor their complex Th2 changed the content of lipid peroxidation products or the level of AOS enzymes in hepatocytes from mice with NK/Ly. BF1 (in concentration 10 mg/kg) and PEG-PN + BF1 complex did not change the level of murine erythrocytes compared to Doxorubicin. All investigated compounds, except free PEG-PN, significantly decreased the NK/Ly-triggered leukocytosis and increased the level of small lymphocytes. The NK/Ly lymphoma development led to an increase in the number of neutrophils, while BF1 and its complex with PEG-PN reduced it significantly. Conclusions. BF1 and PEG-PN + BF1 complex had limited negative side effects in the mice with NK/Ly. The investigated compounds were not hepatotoxic toward murine liver cells. Both BF1 and its complex with PEG-PN did not cause any major side effects on the murine blood cells.


Fig. 1. Structure of thiazole derivative BF1 and polymeric carrier (pc) poly(peGMa-co-DMM) (k = 87% mol, l = 13% mol, M n = 47 kDa)
Fig. 7. the quantitative data of DNa damage in MDa-MB-231 cells after 24 h treatment with doxorubicin (Dox, 0.6 µM), thiazole derivative BF1 (27 µM), complex of BF1 with the pc (BF1-pc, 7 µM), free pc (7 µM), and dimethyl sulfoxide (DMSO, 270 μg/ml corresponding to the solvent concentration of BF1 at 27 µM). *P < 0.05, ***P < 0.001 (significant changes compared with control (untreated) cells). Data are presented as mean ± SD (n = 4). pc, polymeric carrier poly(peGMa-co-DMM)
Fig. 8. Images of MDa-MB-231 cells treated for 24 h with the studied compounds: (G, H) complex of BF1 with the pc (BF1-pc, 7 µM); (I, J) free pc (7 µM); (K, L) dimethyl sulfoxide (DMSO, 270 μg/ml corresponding to the solvent concentration of BF1 at 27 µM). Left images -differential interference contrast (DIC) images of treated cells stained with hoechst-33342 (blue color) and propidium iodide (red color). Right imagesfluorescent images of treated and stained cells. Yellow arrows indicate chromatin condensation in cells, green arrows -chromatin fragmentation, pink arrows -micronucleus, white arrows -blebbing of plasma membrane. Scale bars equal 20 μm. PC, polymeric carrier poly(PEGMA-co-DMM)
Effect of a novel thiazole derivative and its complex with a polymeric carrier on stability of DNA in human breast cancer cells

May 2021

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53 Reads

The Ukrainian Biochemical Journal

Thiazole derivatives are perspective antitumor compounds characterized by a broad range of bioactivity, while polymeric carriers are widely used to enhance the efficiency of biological action of drugs, improve their biocompatibility and water solubility. Previously, we identified that the thiazole-based derivative BF1 (N-(5-benzyl-1,3-thiazol-2-yl)-3,5-dimethyl-1-benzofuran-2-carboxamide) possessed differential toxicity towards targeted tumor cell lines. The aim of the present work was to investigate the action in vitro of BF1 and its complex with the polymeric carrier (PC) poly(PEGMA-co-DMM) (BF1-РС complex) towards human breast adenocarcinoma cells of the MDA-MB-231 and MCF-7 lines. DNA comet analysis, diphenylamine DNA fragmentation assay, gel retardation assay of plasmid DNA, DNA intercalation assay using methyl green dye and fluorescent microscopy were used to study the effects of BF1 on DNA stability in breast cancer cells. The ІС50 of cytotoxic action towards MDA-MB-231 cells was 26.5 ± 2.9 µМ for BF1, while the ІС50 for the BF1-PC complex was 6.9 ± 0.4 µМ, and the PC demonstrated low toxicity (ІС50 ˃ 50 µМ). The BF1-PC complex possessed higher toxicity towards MCF-7 cells than free BF1, with ІС50 of 9.6 ± 0.8 µМ and 15.8 ± 0.9 µМ, respectively. BF1 and BF1-PC induced an increase in the number of damaged cells of the MDA-MB-231 line with blebbing of plasma membrane, condensed chromatin and/or fragmented nucleus and micronuclei formation. Both BF1 and the BF1-PC complex induced single-strand breaks in DNA and its fragmentation in treated MDA-MB-231 cells. The studied compounds were not bound to plasmid DNA and did not intercalate into DNA molecules.





Citations (11)


... Research into thiazole derivatives has shown their potential to modulate ROS levels, suggesting both anti-inflammatory and antioxidant properties. For example, [29] explored the effects of thiazole derivatives complexed with polyethylene glycol (PEG)based nanoparticles on ROS production in NK/Ly lymphoma cells and mouse hepatocytes. Their findings underscore the complex interplay between thiazole derivatives and ROS levels, illustrating the compounds' capabilities to modulate oxidative stress. ...

Reference:

4-Methylthiazole triggers apoptosis and mitochondrial disruption in HL-60 cells
Generation of ROS under the influence of thiazole derivative and its complexes with PEG-based polymeric nanoparticles
  • Citing Article
  • December 2022

Biopolymers and Cell

... As previously established, thiazole derivative BF1 in complex with polymeric nanomicelles based on polyethylene glycol (PEG) poly(PEGMA) (Th3) exhibited a greater level of cytotoxicity towards specific tumor cell lines compare to unconjugated BF1 or/and chemotherapeutic drug Doxorubicin and lead to apoptotic-like changes in lymphoma cells [9]. ...

Antineoplastic Activity In Vitro of 2-amino-5-benzylthiasol Derivative in the Complex with Nanoscale Polymeric Carriers
  • Citing Article
  • February 2021

Cytology and Genetics

... Результати експериментів наведені у таблиці 1. Отже, досліджувані протипухлинні сполуки не інтенсифікують процеси ПОЛ та не впливають на активність ферментів антиоксидантної системи захисту в клітинах печінки мишей з лімфомою. Результати експериментів узгоджуються з попередніми даними, де встановлено, що досліджувані сполуки не були цитотоксичними щодо непухлинних клітин ліній HEK293 та NIH3T3 in vitro та клітин крові мишей з лімфомою in vivo [3,4]. Водночас, згідно з попередніми дослідженнями, БФ1 та її комплекс з ПЕГ-ПН достовірно збільшували вміст продуктів ПОЛ та змінювали активність ферментів антиоксидантного захисту в клітинах лімфоми NK/Ly [5,6]. ...

Safety profile of thiazole derivative and its complex with PEG-based polymeric nanoparticles on liver and blood cells in tumor-bearing mice

Studia Biologica

... DNA intercalation assay using methyl green DNA intercalation assay using methyl green was conducted as described previously [28]. Briefly, 485 µl of salmon sperm DNA (50 μg/ml, Sigma-Aldrich, USA) were incubated for 1 h at 37°C with 15 µl of methyl green solution (1 mg/ml, Sigma-Al-drich, USA). ...

Apoptosis induction in human leukemia cells by novel 2-amino-5-benzylthiazole derivatives

The Ukrainian Biochemical Journal

... Як продовження наших досліджень синтетичного потенціалу діазонієвих солей [19][20][21], реакцій азосполучення [22] та хімії піразолів [23][24][25][26], в цій статті ми представляємо синтез та вивчення фотофізичних властивостей етил 5-ацетил-4-аміно-1-арил-1Н-піразол-3карбоксилатів. ...

Spectrophotometry of 1-(1-methyl-1Н-pyrazol-3-il-azo)-naphtalen-2-ol
  • Citing Article
  • January 2020

Visnyk of the Lviv University Series Chemistry

... Among 2-aminothiazole-based compounds 5benzyl derivatives are of special interest over the last decades. Significant antimicrobal (Khalilet et al., 2015) and anticancer activities of these compounds (Krasavin et al., 2009;Pokhodylo et al., 2014;Choi et al., 2011;Schiedel et al., 2016;Finiuk et al., 2017;Ostapiuk et al., 2018) have been reported. Aminothiazole derivatives have been also used as sensitive analytical reagents (Lozynska et al., 2015;Tymoshuk et al., 2019). ...

Synthesis and antitumor activities of new N-(5-benzylthiazol-2-yl)-2-(heteryl-5-ylsulfanyl)-acetamides
  • Citing Article
  • February 2018

Biopolymers and Cell

... Як продовження наших досліджень синтетичного потенціалу діазонієвих солей [19][20][21], реакцій азосполучення [22] та хімії піразолів [23][24][25][26], в цій статті ми представляємо синтез та вивчення фотофізичних властивостей етил 5-ацетил-4-аміно-1-арил-1Н-піразол-3карбоксилатів. ...

Evaluation of antiproliferative activity of pyrazolothiazolopyrimidine derivatives

The Ukrainian Biochemical Journal

... Compounds 1-3, 1 a-c, 3 a-b, and 6 a-b showed low basal toxicity towards mammalian cells (CC 50 � 100 μM), [38] while 2 b, 4 a, 4 c and 5 b were weakly toxic (50 μM � CC 50 � 100 μM) [39] and 4-6, 2 a, and 4 b were mild to moderately toxic (10 μM � CC 50 � 50 μM). [39,40] The synthesized compounds generally showed poor trypanocidal activity against the investigated human and animal infective trypanosome species, and only derivatives 1 b, 3 a, 4 a- Table 1. Growth inhibition (%) of compounds at 10 μM against T. cruzi strain CL epimastigotes and trypomastigotes. ...

Antineoplastic activity of novel thiazole derivatives

Biopolymers and Cell

... However, the best results were observed Paper by using nitrosylsulfuric acid for diazotization of 2-amino-4methyl-5-(4-sulfonamidobenzyl)thiazole. 37 5-Aryl-1,3-thiazole-2-diazonium salts are unstable, but they react in a diazocoupling reaction efficiently. In conclusion, SABnMeTAN was synthesized by diazotization of 2-amino-4methyl-5-(4-sulfonamidobenzyl)thiazole and subsequent treatment under diazocoupling conditions. ...

ChemInform Abstract: Convenient Synthesis of α-Bromo Ketones by the Meerwein Reaction.

Russian Journal of Organic Chemistry

... 3-Aryl-2-chloropropanals (2a-d) react with the thiourea in ethanol at refluxing and form 2-amino-5-R-benzyl-1,3thiazoles (3a-d) with good yield [22,23]. Previously, we have discussed the synthetic possibilities of 5-benzyl-2-aminothiazoles during the synthesis of 2-[(5-benzyl-1,3-thiazol-2-yl)imino]-1,3-thiazolidin-4-ones as potential biologically active compounds [24,25]. In this paper, we described N-acylated 2-amino-5-benzyl-1,3-thiazoles (5a-d) obtained by the reaction of 2-amino-5-R-benzyl-1,3-thiazoles 3a-d with acid chlorides 4a-d in the presence of trietylamine in the dioxane medium. ...

Synthesis of heterocycles on the basis of products of arylation of unsaturated compounds 22.* 3-Aryl-2-chloropropanal in the synthesis of N-Aryl-5-(R-benzyl)-1,3-thiazole-2-amines
  • Citing Article
  • August 2010

Chemistry of Heterocyclic Compounds