Biopolym. Cell. 2022; 38(3):158-168.
Structure and Function of Biopolymers
Generation of ROS under the influence of thiazole derivative and its complexes with PEG-based polymeric nanoparticles
1Ilkiv M. V., 1Shalai Ya. R., 1Manko B. O., 1Ostapiuk Yu. V., 2Mitina N. E., 2Zaichenko A. S., 1Babsky A. M.
  1. Ivan Franko National University of Lviv
    4, Hrushevskoho Str., Lviv, Ukraine, 79005
  2. Lviv Polytechnic National University
    12, S. Bandery Str., Lviv, Ukraine, 79013


Aim. To determine the in vitro effect of thiazole derivative and its complex with polyethylene glycol (PEG)-based nanoscale particles on ROS generation in the NK/Ly lymphoma cells and hepatocytes of mice. Methods. The effects of BF-1 (N-(5-benzyl-1,3-thiazol-2-yl)-3,5-dimethyl-1-benzofuran-2-carboxamide), PEG-based polymeric nanoparticles (Th1, Th3, Th5) and their complexes (Th2, Th4, Th6) on ROS production in murine NK/Ly lymphoma cells were studied using fluorescent microscopy. The level of superoxide in both murine hepatocytes and NK/Ly cells was determined with a spectrophotometric assay. Results. BF1, Th2, Th6 and Th5 significantly increased the level of ROS in NK/Ly lymphoma cells [-] by 27.7 %, 28.6 % 22.7 % and 20.1 %, respectively. Meanwhile, Th1, Th3, Th4 did not affect the ROS level. The level of superoxide significantly decreased under the influence of BF1 by 14.7 % and all its complexes with PEG-based polymeric nanoparticles (Th2, Th4, Th6) by 25.5 %, 21.6 % and 13 %, respectively, compared to control. Unlike lymphocytes, in the murine hepatocytes none of the investigated compounds affected the superoxide content. Conclusions. Thus, thiazole derivative BF1 may realize its antitumor effect on cancer cells by promoting generation of additional amount of ROS. BF1 and its complexes with PEG-containing polymeric nanoparticles significantly increase the ROS generation in NK/Ly cells. Meanwhile, all investigated compounds did not change the level of superoxide in murine hepatocytes. It can be evidence of their low toxicity to nontumor cells.
Keywords: thiazole derivative, polyethylene glycol, polymeric nanoparticles, ROS, superoxide radical


[1] Kumari S, Badana AK, G MM, G S, Malla R. Reactive oxygen species: a key constituent in cancer survival. Biomarker insights. 2018; 13: 1177271918755391.
[2] Cheung EC, Vousden KH. The role of ROS in tumour development and progression. Nat Rev Cancer. 2022; 22(5):280-97.
[3] Redza-Dutordoir M, Averill-Bates D. Activation of apoptosis signalling pathways by reactive oxygen species. Biochim Biophys Acta. 2016; 1863(12):2977-92.
[4] Finiuk N, Klyuchivska O, Ivasechko I, Hreniukh V, Ostapiuk Yu, Shalai Ya, Panchuk R, Matiychuk V, Obushak M., Stoika R, Babsky A. Proapoptotic effects of novel thiazole derivative on human glioma cells. Anti-cancer Drugs. 2019; 30(1):27-37.
[5] Patra J, Das G, Fraceto L, Campos E, Rodriguez-Torres M, Acosta-Torres L, Diaz-Torres L, Grillo R, Swamy M, Sharma S, Habtemariam S, Shin H. Nano based drug delivery systems: recent developments and future prospects. J Nanobiotechnol. 2018; 16(1):71.
[6] Sim S, Wong NK. Nanotechnology and its use in imaging and drug delivery (Review). Biomed Rep. 2021; 14(5):42.
[7] Finiuk N, Popovych M, Shalai Y, Mandzynets' S, Hreniuh V, Ostapiuk Y, Obushak M, Mitina N, Zaichenko O, Stoika R, Babsky A. Antineoplastic activity in vitro of 2-amino-5-benzylthiasol derivative in the complex with nanoscale polymeric carriers. Cytol Genet. 2021; 55(1):19-27.
[8] Popovych M, Shalai Ya, Hreniukh V, Kulachkovskyy O, Mandzynets S, Mitina N, Zaichenko O, Babsky AM. Effect of thiazole derivative complexed with nanoscale polymeric carriers on cellular ultrastructure of murine lymphoma cells in vivo. Studia Biologica. 2021; 15(2):15-24.
[9] Popovych M, Shalai Ya, Mandzynets S, Mitina N, Zaichenko O, Babsky A. Effect of a novel thiazole derivative and its complex with polymeric carriers on the activity of antioxidant enzymes in murine lymphoma cells. Studia Biologica. 2021; 15(4): 37-48.
[10] Mitina NYe, Riabtseva AO, Garamus VM, Lesyk RB, Volyanyuk KA, Izhyk OM, Zaichenko OS. Morphology of the micelles formed by a comb-like PEG-containing copolymer loaded with antitumor substances with different water solubilities. Ukr J Phys. 2020; 65(8):670-7.
[11] Shlykov SG, Babich LG, Yevtushenko ME, Karakhim SO, Kosterin SO. Modulation of myometrium mitochondrial membrane potential by calmodulin antagonists. Ukr Biochem J. 2014; 86(1):29-41.
[12] Denisenko S, Kostenko V. Changes in the production of reactive oxygen species in the testes of white rats under conditions of chronic intoxication with sodium nitrate. Modern Problems Toxicology. 2002; 4: 44-46.
[13] Finiuk NS, Hreniuh VP, Ostapiuk YuV, Matiychuk VS, Frolov DA, Obushak MD, Stoika SR, Babsky AM. Antineoplastic activity of novel thiazole derivatives. Biopolym Cell. 2017; 33(2):135-46.
[14] Cuong NV, Jiang JL, Li YL, Chen JR, Jwo SC, Hsieh MF. Doxorubicin-loaded PEG-PCL-PEG micelle using Xenograft model of nude mice: effect of multiple administration of micelle on the suppression of human breast cancer. Cancers (Basel). 2010; 3(1):61-78.
[15] Xu Q, Chu CC. Development of ROS-responsive amino acid-based poly(ester amide) nanoparticle for anticancer drug delivery. J Biomed Mater Res A. 2021; 109(4):524-37.
[16] Jena N. DNA damage by reactive species: mechanisms, mutation and repair. J Biosci. 2012; 37(3):503-7.
[17] Yang F, Teves S, Kemp C, Henikoff S. Doxorubicin, DNA torsion, and chromatin dynamics. Biochim Biophys Acta. 2014; 1845(1): 84-9.
[18] Rhee S. A catalytic career: Studies spanning glutamine synthetase, phospholipase C, peroxiredoxin, and the intracellular messenger role of hydrogen peroxide. J Biol Chem. 2019; 294(13): 5169-80.