In vitro and in vivo protein synthesis inhibition by methylated derivatives of 4-oxypiperidine-1-oxyl.

A new Soviet experimental antioxidant, nitroxyl-2 (2,2,6,6-tetramethyl 4-oxypiperidine 1-oxyl), is a potent inhibitor of protein synthesis in vivo (mouse liver) and in vitro (reticulocyte lysate). Demethylated derivatives of this agent demonstrate a significantly lower inhibitory activity. The HPLC estimation of ATP/ADP ratio in a mouse liver tissue homogenate shows that nitroxyl-2 and its demethylated derivatives possess a similar antioxidant effect. In cell-free translation, the drugs have no effect on the ATP/ADP ratio. The acute drug toxicity (LD50 and the protein synthesis inhibitory activity in vivo (ID50) and in vitro (IC50) were determined and were shown to be highly correlated with the number of methyl groups of the drug molecule. These results are discussed.