Tag Archives: thiazole derivative

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;
e-mail: popovych.marta@gmail.com

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.

Effect of a novel thiazole derivative and its complex with a polymeric carrier on stability of DNA in human breast cancer cells

N. S. Finiuk1,2, O. Yu. Klyuchivska1, I. I. Ivasechko1,
N. E. Mitina3, Yu. V. Ostapiuk2, M. D. Obushak2,
O. S. Zaichenko3, A. M. Babsky2, R. S. Stoika1,2*

1Institute of Cell Biology, NAS of Ukraine, Lviv, Ukraine;
2Ivan Franko National University of Lviv, Lviv, Ukraine;
3Lviv Polytechnic National University, Lviv, Ukraine;
*e-mail: stoika.rostyslav@gmail.com

Received: 26 January 2021; Accepted: 2021

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.