Thioether derivatives of 1,2,3-triazole-N-oxides: Synthesis, study of cytotoxicity and cellular nitric oxide (NO) production effect

Abstract

In this work, a synthetic strategy based on the reaction of 5-bromo-2-(4-fluorophenyl)-4-methyl-2H-1,2,3-triazole with various thioaromatic derivatives were applied to afford a series of thioether derivatives of 1,2,3-triazole-N-oxides in yields of 52–80%. The obtained compounds were shown to be characterized by low cytotoxicity towards human embryonic kidney (HEK293) cells with IC50 values ranging from 128 to 76 µM and high toxicity towards malignant rhabdomyosarcoma cancer (Rd) cells with IC50 values ranging from 93 to 22 µM. These compounds were screened for the ability to induce nitric oxide production in cells via DAF-FM fluorescence. Several compounds demonstrated a twofold increase in nitric oxide levels relative to the control. Two leader molecules demonstrating the lowest cytotoxicity values and the effect on nitric oxide production in rhabdomyosarcoma cells were identified. Thus, the method could be considered as a convenient one for qualitative or semi-quantitative determination of nitric oxide in a screening process of large number of compounds to define lead molecules capable of influencing nitric oxide production.