Tag Archives: thiazole derivatives

Prooxidant and antioxidant processes in the liver homogenate of healthy and tumor-bearing mice under the action of thiazole derivatives

Ya. R. Shalai1*, M. V. Popovych1, S. M. Mandzynets1,
V. P. Hreniukh1, N. S. Finiuk1,2, A. M. Babsky1

1Ivan Franko National University of Lviv, Ukraine;
2Institute of Cell Biology, National Academy of Sciences of Ukraine, Lviv;
*e-mail: Yaryna.Shalay@lnu.edu.ua

Received: 12 October 2021; Accepted: 17 May 2021

Thiazole derivatives were shown to have toxic effects in vitro on cancer cells of different origin and can be considered as potentially antineoplastic, but their effect on the normal tissues needs to be studied. In this research the newly synthesized thiazole derivatives of N-(5-benzyl-1,3-thiazol-2-yl)-3,5-dimethyl-1-benzo-furan-2-carboxamide (BF1) and 8-methyl-2-Me-7-[trifluoromethyl-phenylmethyl]-pyrazolo [4,3-e] [1,3] thiazolo [3,2-a] pyrimidin-4 (2H)-one (PP2) were used and their effect on the pro- and antioxidant processes after adding in a 1, 10 and 50 μM concentrations to the liver homogenate of healthy and NK/Ly lymphoma-bearing mice was estimated. The level of superoxide radical and TBA-active products as well as catalase, SOD and glutathione peroxidase activity were measured. It was shown that superoxide radical and TBA-active products­ level and catalase activity were significantly higher in the liver of tumor-bearing mice than in the liver of the healthy mice. Neither BF1 no PP2 influenced the studied indices in the liver homogenate of healthy and tumor-bearing animals with the exception that PP2 significantly reduced the level of TBA-positive products in both cases. The data obtained showed that the studied thiazole derivatives did not cause severe liver toxicity in both healthy and tumor-bearing mice.

Effects of thiazole derivatives on intracellular structure and functions in murine lymphoma cells

V. P. Hreniukh1, N. S. Finiuk1,2, Ya. R. Shalai1, B. O. Manko1,
B. V. Manko1, Yu. V. Ostapiuk1, O. R. Kulachkovskyy1,
M. D. Obushak1, R. S. Stoika1,2, A. M. Babsky1*

1Ivan Franko National University of Lviv, Ukraine;
2Institute of Cell Biology, Nationl Academy of Sciences of Ukraine, Lviv;
*e-mail: andriy.babsky@gmail.com

Received: 22 December 2019; Accepted: 27 March 2020

Thiazole derivatives have cytotoxic effects towards tumor cells, such as glioblastoma, melanoma, leukemia and lymphoma. However, the intracellular mechanism of this action is not clear. The aim of our study was to investigate the action of N-(5-benzyl-1,3-thiazol-2-yl)-3,5-dimethyl-1-benzofuran-2-carboxamide (BF1) and 7-benzyl-8-methyl-2-propylpyrazolo[4,3-e]thiazolo[3,2-a]pyrimidin-4(2H)-one (PP2) on cellular structure, and bioenergetic functions of mitochondria in Nemeth-Kellner lymphoma cells (NK/Ly). The structure of treated NK/Ly cells and their mitochondria was examined using electron microscopy. The rate of oxygen uptake by isolated mitochondria was recorded by a polarographic method using a Clark electrode. The mitochondrial potential relative values were registered using fluorescence dye rhodamine 123. In the short-term (15 min), incubation with BF1 and PP2 in 10 and 50 µM concentrations induced apoptotic and necrotic changes in the structure of NK/Ly cells, such as fragmentation and disintegration of the nucleus, destruction of the plasma membrane, and an increase in numbers of lysosomes and mitochondria. A polarographic method did not show significant metabolic shifts in lymphoma mitochondria, in either in vitro or ex vivo actions of the thiazole derivatives. However, fluorescent microscopy showed a significant decrease in mitochondria potential, following a 15 min incubation of cells with 50 µM of PP2. Thus, the electron and fluorescent microscopy data suggest that mitochondria are involved in the mechanism of cytotoxic action of the studied thiazole derivatives.