Effect of novel 2-amino-5-benzylthiazole derivative on cellular ultrastructure and activity of antioxidant system in murine lymphoma cells

The influence of newly synthesized thiazole derivative N-(5-benzyl-1,3-thiazol-2-yl)-3,5-dimethyl-1-benzofuran-2-carboxamide on cellular ultrastructure and anti­oxidant system activity in lymphoma cells was studied in vitro. A pronounced cytotoxic action of the newly synthesized thiazole derivative on the tumor cells in vitro was reported earlier. However, no cytotoxicity of this substance was detected toward non-cancerous cells. In addition, it was shown that the scavengers of active forms of Oxygen significantly reduced a cytotoxic effect of the studied compound. It was found that thiazole derivatives at concentrations of 10 and 50 M affected the level of lipid peroxidation products and superoxide radicals. The purpose of this work was to investigate the effect of N-(5-benzyl-1,3-thiazol-2-yl)-3,5-dimethyl-1-benzofuran-2-carboxamide on the ultrastructure of lymphoma cells and the activity of enzymes of the antioxidant defense. The influence of the thiazole derivatives on cellular ultrastructure of lymphoma cells was investigated. Еlectron microscopy study show that control lymphoma cells have a special subcellular formations such as a relatively large nucleus, and specific plasma membrane filaments. The effects of thiazole derivative at concentrations of 10 and 50 M revealed apoptotic and necrotic manifestations of cytotoxicity, such as a deformation and disintegration of nucleus, an increased area and number of lysosomes, a destruction of the plasma membrane and a change of mitochondria shape. The effect of the thiazole derivative on the activity of key enzymes of the antioxidant system in lymphoma cells was investigated. The studied compound at concentrations of 10 and 50 M activate superoxide dismutase and lead to a decrease of the activity of catalase and glutathione peroxidase. This effect suggests that the change in the activity of enzymes leads to accumulation of H2O2 in the lymphoma cells. Such results indicate that the studied substance can realize its cytotoxic effect through the action of the antioxidant system. The obtained data can be used to carry out further preclinical studies of the thiazole derivatives as potential antitumor drugs.