The semisynthetic spin-labelled derivatives of 3-hydroxybutanolide as potential oxidative stress inhibitors.

To obtain more accessible oxidative stress inhibitors, a series of novel spin-labelled derivatives of 3-hydroxybutanolide (2a-d, 3a-d) with the natural active compound (kinsenoside) as the lead compound were designed, synthesised from the nitroxide free radical piperidine (pyrroline) and the main structural unit of kinsenoside: 3-hydroxybutanolide. Antioxidant activity screening of these derivatives was performed using MTT method on rat pheochromocytoma PC12 cells. The antioxidative stress effect was further investigated on the changes of the important antioxidant enzyme activities and intracellular reactive oxygen species production. Among the derivatives, 2b-d, 3a and 3c showed comparable or superior antioxidative stress activity to kinsenoside. Also, most of the tested derivatives displayed obvious antioxidative ability in concentrations. Cytotoxic assay simultaneously indicated that all compounds had very low toxicity to normal cells. Based on the observed results, the structure-activity relationship of these derivatives was discussed.