Cytotoxicity of new platinum complexes based on 3-(2-pyridyl)-1,2,4-triazole derivatives against squamous cell carcinoma

Platinum complexes are one of the key elements of anti-tumor chemotherapy. Currently, the efforts are focused on the development of novel Pt-complexes based on ligands of various chemical nature. The aim of the research was to study the anticancer activity of new platinum complexes based on ligands 2-(5-ethyl-1-methyl-1H-1,2,4-triazol-3-yl)pyridine (L 6 ) and benzyl (2-(5-benzyl-1-methyl-1H-1,2,4-triazol-3-yl)pyridine (L 12). Methods.The cytotoxicity of the Pt(L 6 )Cl 2 and Pt(L 12 )Cl 2 complexes against the Hep-2 and MAEC cells was assessed.The catalytic activities of lactate dehydrogenase (LDH), succinate dehydrogenase (SDH), and glucose-6-phosphate dehydrogenase (G6PD) were determined using the nitroblue tetrazolium assay.The intracellular ROS level was determined by the 2',7'-dichlorofluorescein diacetate, and the mitochondrial potential (ΔΨ m ) was determined by Rhodamine 123.Results.The calculated EC 50 for Pt(L 12 )Cl 2 against Hep-2 cells was 9.12 ± 0.33 μM.The LDH activity was decreased in both Hep-2 and MAEC cells, but no changes in the SDH activity were detected in Hep-2 cells.In Hep-2 cells, the treatment with the Pt(L 12 )Cl 2 complex resulted in decrease in G6PD activity, whereas the Pt(L 6 )Cl 2 complex induced increase.An increase in the ΔΨ m and ROS was observed in Hep-2 cell.Conclusions.The Pt complexes have a cytotoxic effect on Hep-2 cells by reducing the activity of LDH, but without affecting SDH.Intracellular ROS level was changed weak, but ΔΨ m was increased.