Ukr.Biochem.J. 2022; Volume 94, Issue 6, Nov-Dec, pp. 30-36


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

M. V. Ilkiv1, Ya. R. Shalai1, H. M. Mazur1, B. O. Manko1,
B. V. Manko1, Yu. V. Ostapiuk2, N. E. Mitina3,
A. S. Zaichenko3, A. M. Babsky1

1Biology Faculty, Ivan Franko National University of Lviv, Ukraine;
2Chemistry Faculty, Ivan Franko National University of Lviv, Ukraine;
3Institute of Chemistry and Chemical Technologies,
Lviv Polytechnic National University, Ukraine;

Received: 27 September 2022; Revised: 01 December 2022;
Accepted: 17 February 2023; Available on-line: 27 February 2023

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: , , , , ,


  1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72(1):7-33. PubMed, CrossRef
  2. Chen XS, Li LY, Guan YD, Yang JM, Cheng Y. Anticancer strategies based on the metabolic profile of tumor cells: therapeutic targeting of the Warburg effect. Acta Pharmacol Sin. 2016;37(8):1013-1019. PubMed, PubMedCentral, CrossRef
  3. Ghanbari Movahed Z, Rastegari-Pouyani M, Mohammadi MH, Mansouri K. Cancer cells change their glucose metabolism to overcome increased ROS: One step from cancer cell to cancer stem cell? Biomed Pharmacother. 2019;112:108690. PubMed, CrossRef
  4. Fadaka A, Ajiboye B, Ojo O, Adewale O, Olayide I, Emuowhochere R. Biology of glucose metabolization in cancer cells. J Oncol Sci. 2017;3(2):45-51. CrossRef
  5. Liu Y, Shi Y. Mitochondria as a target in cancer treatment. MedComm. 2020;1(2):129-139. PubMed, PubMedCentral, CrossRef
  6. Kapur A, Mehta P, Simmons AD, Ericksen SS, Mehta G, Palecek SP, Felder M, Stenerson Z, Nayak A, Dominguez JMA, Patankar M, Barroilhet LM. Atovaquone: An Inhibitor of Oxidative Phosphorylation as Studied in Gynecologic Cancers. Cancers (Basel). 2022;14(9):2297. PubMed, PubMedCentral, CrossRef
  7. Wen S, Zhu D, Huang P. Targeting cancer cell mitochondria as a therapeutic approach. Future Med Chem. 2013;5(1):53-67. PubMed, PubMedCentral, CrossRef
  8. Li Q, Huang Y. Mitochondrial targeted strategies and their application for cancer and other diseases treatment. J Pharm Investig. 2020;50:271-293. CrossRef
  9. Alizadeh SR, Hashemi SM. Development and therapeutic potential of 2-aminothiazole derivatives in anticancer drug discovery. Med Chem Res. 2021;30(4):771-806. PubMed, PubMedCentral, CrossRef
  10. Elsadek MF, Ahmed BM, Farahat MF. An Overview on Synthetic 2-Aminothiazole-Based Compounds Associated with Four Biological Activities. Molecules. 2021;26(5):1449. PubMed, PubMedCentral, CrossRef
  11. Wan Y, Long J, Gao H, Tang Z. 2-Aminothiazole: A privileged scaffold for the discovery of anti-cancer agents. Eur J Med Chem. 2021;210:112953. PubMed, CrossRef
  12. Bestgen B, Krimm I, Kufareva I, Kamal AAM, Seetoh WG, Abell C, Hartmann RW, Abagyan R, Cochet C, Le Borgne M, Engel M, Lomberget T. 2-Aminothiazole Derivatives as Selective Allosteric Modulators of the Protein Kinase CK2. 1. Identification of an Allosteric Binding Site. J Med Chem. 2019;62(4):1803-1816. PubMed, PubMedCentral, CrossRef
  13. Ouyang B, Wang L, Qi J, Fan M, Wang H, Yao L. Synthesis and Evaluation of Biological Properties of 2-Amino-thiazole-4-carboxamides: Amide Linkage Analogues of Pretubulysin. Biol Pharm Bull. 2020;43(8):1154-1158. PubMed, CrossRef
  14. Ostapiuk YV, Ostapiuk MY, Barabash OV, Kravets M, Herzberger C, Namyslo JC, Obushak MD, Schmidt A. One-pot syntheses of substituted 2 aminothiazoles and 2-aminoselenazoles via Meerwein arylation of alkyl vinyl ketones. Synthesis. 2022;54(16):3658-3666. CrossRef
  15. Ostapiuk YV, Barabash OV, Ostapiuk MY, Goreshnik E, Obushak MD, Schmidt A. Thiocyanatoarylation of Methyl Vinyl Ketone under Meerwein Conditions for the Synthesis of 2-Aminothiazole-Based Heterocyclic Systems. Org Lett. 2022;24(25):4575-4579. PubMed, CrossRef
  16. Finiuk NS, Hreniuh VP, Ostapiuk YuV, Matiychuk VS, Frolov DA, Obushak MD, Stoika RS, Babsky AM. Antineoplastic activity of novel thiazole derivatives. Biopolym Cell. 2017;33(2):135-146. CrossRef
  17. 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. Anticancer Drugs. 2019;30(1):27-37. CrossRef
  18. Hreniukh VP, Finiuk NS, Shalai YaR, Manko BO, Manko BV, Ostapiuk YuV, Kulachkovskyy OR, Obushak MD, Stoika RS, Babsky AM. Effects of thiazole derivatives on intracellular structure and functions in murine lymphoma cells. Ukr Biochem J. 2020; 92(2): 121-130. CrossRef
  19. Shalai YaR, Popovych MV, Kulachkovskyy OR, Hreniukh VP, Mandzynets SM, Finiuk NS, Babsky AM. Effect of novel 2-amino-5-benzylthiazole derivative on cellular ultrastructure and activity of antioxidant system in lymphoma cells. Studia Biologica. 2019; 13(1): 51-60. CrossRef
  20. Kozak MR, Ostapiv DD, Mitina NY, Petruh IM, Volianiuk KA, Zaichenko AS, Vlizlo VV. An influence of complexes of therapeutic antisense oligodeoxynucleotides with cationic polymers on cell respiration. Biopolym Cell. 2021; 37(5): 357-368. CrossRef
  21. Finiuk NS, Popovych MV, Shalai YaR, Mandzynets’ SM, Hreniuh VP, Ostapiuk YuV, Obushak MD, Mitina NE, Zaichenko OS, Stoika RS, Babsky AM. Antineoplastic activity in vitro of 2-amino-5-benzylthiasol derivative in the complex with nanoscale polymeric carriers. Cytol Genet. 2021;55(1):19–27.
  22. 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 Physics. 2020;65(8):670. CrossRef
  23. Horbay RO, Manko BO, Manko VV, Lootsik MD, Stoika RS. Respiration characteristics of mitochondria in parental and giant transformed cells of the murine Nemeth-Kellner lymphoma. Cell Biol Int. 2012;36(1):71-77. PubMed, CrossRef
  24. Moldogazieva NT, Mokhosoev IM, Terentiev AA. Metabolic Heterogeneity of Cancer Cells: An Interplay between HIF-1, GLUTs, and AMPK. Cancers (Basel). 2020;12(4):862. PubMed, PubMedCentral, CrossRef
  25. Fogg VC, Lanning NJ, Mackeigan JP. Mitochondria in cancer: at the crossroads of life and death. Chin J Cancer. 2011;30(8):526-539. PubMed, PubMedCentral, CrossRef
  26. Kuznetsov AV, Margreiter R, Amberger A, Saks V, Grimm M. Changes in mitochondrial redox state, membrane potential and calcium precede mitochondrial dysfunction in doxorubicin-induced cell death. Biochim Biophys Acta. 2011;1813(6):1144-1152. PubMed, CrossRef
  27. Galluzzi L, Larochette N, Zamzami N, Kroemer G. Mitochondria as therapeutic targets for cancer chemotherapy. Oncogene. 2006;25(34):4812-4830. PubMed, CrossRef
  28. Zhao RZ, Jiang S, Zhang L, Yu ZB. Mitochondrial electron transport chain, ROS generation and uncoupling (Review). Int J Mol Med. 2019;44(1):3-15. PubMed, PubMedCentral, CrossRef

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License.