Background. Previous studies have shown a pronounced cytotoxic effect of thiazole derivatives in combination with polymeric carriers on tumor cells. At the same time, the derivatives were not cytotoxic against non-cancerous cells in vitro. It was shown that thiazole derivatives at concentrations of 10 and 50 μM affected the prooxidant and antioxidant systems of lymphoma cells in vitro. The aim of this work was to study the effect of the complex of thiazole derivative N-(5-benzyl-1,3-thiazol-2-yl)-3,5-dimethyl-1-benzofuran-2-carboxamide (BF1) in combination with polymeric carriers poly(VEP-co-GMA)-graft-mPEG (Th1), poly(PEGMA) (Th3) and poly(PEGMA-co-DMM) (Th5) on the antioxidant defense system of the NK/Ly cell in vitro. Materials and Methods. The experiments were performed on white wild-type male mice with grafted NK/Ly lymphoma. Tumor cells were inoculated into mice intraperitoneally. Ascites was drained from the abdominal cavity of anaesthetized mice with a sterile syringe on the 7th-10th day after inoculation. Investigated compounds BF1, BF1 + Th1 (Th2, Th12), BF1 + Th3 (Th4, Th14), BF1 + Th5 (Th6, Th16) at a final concentration of 10 μM were added to the lymphoma samples and incubated for 10 min; the activity of antioxidant enzymes was determined according to the techniques described previously. Results. It was found that all the studied complexes based on thiazole derivative BF1 and polymeric carriers poly (VEP-co-GMA)-graft-mPEG (Th2, Th12), poly (PEGMA) (Th4, Th14) and poly (PEGMA-co-DMM) (Th6, Th16) at a concentration of 10 μm increased the activity of SOD, while the activity of CAT and GPX were reduced compared to control. Complexes Th2, Th12 and Th4 increased the significance of the BF1 influence on lymphoma cells from P <0.05 to P <0.01. Pure polymeric carriers did not affect the level of the antioxidant defense system enzymes. Conclusions. Thus, it was found that the polymeric carriers in combination with thiazole derivative BF1 increased the significance of thiazole derivative BF1 influence on the activity of the antioxidant defense system of lymphoma cells, while pure polymeric carriers did not affect the activity of SOD, CAT or GPX. The results of this work can be used for further studies of complexes of thiazole derivative and PEG-containing polymeric carriers as potential antitumor drugs.
Effect of a novel thiazole derivative and its complex with polymeric carriers on the activity of antioxidant enzymes in murine lymphoma cells
