Antineoplastic Activity In Vitro of 2-amino-5-benzylthiasol Derivative in the Complex with Nanoscale Polymeric Carriers

Finiuk, Nataliya; Popovych, M. V.; Shalai, Ya. R.; Mandzynets, S. М.; Hreniuh, V. P.; Ostapiuk, Yu. V.; Обушак, Н. Д.; Mitina, Nataliya; Зайченко, О. С.; Stoika, Rostyslav; Babsky, Andriy M.

doi:10.3103/s0095452721010084

Cited by 9 publications

(7 citation statements)

References 25 publications

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“…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].…”

Section: Introductionmentioning

confidence: 83%

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

Omeliukh,

Shalai,

Bura

et al. 2023

Bìol. Tvarin

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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.

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Section: Introductionmentioning

confidence: 83%

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

Omeliukh,

Shalai,

Bura

et al. 2023

Bìol. Tvarin

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“…The thiazole deriva tive BF1 (N(5benzyl1,3thiazol2yl)3,5dime thyl1benzofuran2carboxamide) was synthesized at the Department of Organic Chemistry of Ivan Franko National University of Lviv and used for preparing of initial 10 mM solution of BF1 in dime thyl sulfoxide [15,18]. The PEGPN Th1 (full name: poly(VEPcoGMA)graft-mPEG k = 1.4% mol, l = 98.6% mol, M n = 240 kDa) was synthesized at the Department of Organic Chemistry of the Lviv Polytechnic National University, as described earlier [21,22].…”

Section: Methodsmentioning

confidence: 99%

“…It was shown, that influence of poly ethylene glycolcontaining surfactants changed cell respiration in different types of diseases [2,20]. It was previously established, that the studied com plexes were more cytotoxic to certain tumor cell lines compared to the control than unconjugated BF1 [21].…”

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confidence: 95%

Bioenergetic characteristics of the murine Nemeth-Kellner lymphoma cells exposed to thiazole derivative in complex with polymeric nanoparticles

Popovych¹,

Shalai²,

Mazur³

et al. 2023

Ukr.Biochem.J.

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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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“…In this study, we created a water-soluble form of novel kinase inhibitor, MI-1. To reach this goal, we immobilized MI-1 on the polymeric carrier poly (PEGMA-co-DMM) (M5) which demonstrated its effectiveness in the delivery of the experimental anticancer agent-thiazole derivative N-(5-benzyl-1,3-thiazol-2-yl)-3,5-dimethyl-1-benzofuran-2-carboxamide [33]. In order to approve the anticancer action in vitro of the created complex of MI-1 immobilized on the poly (PEGMA-co-DMM) carrier, a set of experiments aimed at the investigation of cellular and molecular mechanisms of the antineoplastic action of this complex were conducted with targeting human colon carcinoma cells of HCT116 line.…”

Section: Introductionmentioning

confidence: 99%

Antineoplastic Activity of Water-Soluble Form of Novel Kinase Inhibitor 1-(4-Chlorobenzyl)-3-chloro-4-(3-trifluoromethylphenylamino)-1H-pyrrole-2,5-dione immobilized on Polymeric Poly(PEGMA-co-DMM) Carrier

et al. 2022

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The maleimide derivative 1-(4-chlorobenzyl)-3-chloro-4-(3-trifluoromethylphenylamino)-1H-pyrrole-2,5-dione (MI-1) was synthesized as inhibitor of several protein kinases, however, its application is hindered by its poor water solubility. In this study, the mechanisms of the antineoplastic action of MI-1 and its MI-1/M5 complex with M5 carrier (poly (PEGMA-co-DMM)) towards human colon carcinoma HCT116 cells were investigated by using the MTT and clonogenic assays, DNA intercalation with methyl green replacement, alkaline DNA comet assay, and Western-blot analysis. MI-1 compound and its MI-1/M5 complex possessed high toxicity towards colon (HCT116), cervical (HeLa) carcinoma cells and melanoma (SK-MEL-28) cells with GI50 value in a range of 0.75–7.22 µg/mL, and demonstrated high selectivity index (SI ˃ 6.9). The p53 status of colon cancer cells did not affect the sensitivity of these cells to the treatment with MI-1 and its MI-1/M5 complex. M5 polymer possessed low toxicity towards studied cells. The MI-1, MI-1/M5, and M5 only slightly inhibited growth of the pseudo-normal HaCaT and Balb/c 3T3 cell lines (GI50 ˃ 50 μg/mL). The MI-1 and its MI-1/M5 complex induced mitochondria-dependent pathway of apoptosis, damage of the DNA, and morphological changes in HCT116 cells, and affected the G2/M transition checkpoint. The MI-1 intercalated into the DNA molecule, while such capability of MI-1/M5 complex and M5 polymer was much lower. Thus, poly (PEGMA-co-DMM) might be a promising carrier for delivery of the maleimide derivative, MI-1, a novel kinase inhibitor, through improving its solubility in aqueous media and enhancing its antiproliferative action towards human tumor cells. Studies are in progress on the treatment of Nemeth-Kellner lymphoma (NK/Ly)-bearing mice with the MI-1 and MI-1/M5 complex.

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Antineoplastic Activity In Vitro of 2-amino-5-benzylthiasol Derivative in the Complex with Nanoscale Polymeric Carriers

Cited by 9 publications

References 25 publications

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

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

Bioenergetic characteristics of the murine Nemeth-Kellner lymphoma cells exposed to thiazole derivative in complex with polymeric nanoparticles

Antineoplastic Activity of Water-Soluble Form of Novel Kinase Inhibitor 1-(4-Chlorobenzyl)-3-chloro-4-(3-trifluoromethylphenylamino)-1H-pyrrole-2,5-dione immobilized on Polymeric Poly(PEGMA-co-DMM) Carrier

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