A Comparative study on the free radical scavenging reactivity of edaravone and its derivatives

Hata, Kuniki ; Katsumura, Yosuke; Lin, M.; Muroya, Yusa*; Fu, H.*; Yamashita, Shinichi; Kudo, Hisaaki*; Nakagawa, Keiichi*; Nakagawa, Hidehiko*

Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), which is clinically used for brain infarct in Japan from 2001, is a potent antioxidative medicine. Edaravone is also expected as a radioprotector for its high reactivity towards oxidizing radicals. Recently, some edaravone derivatives have been being investigated in order to study the Structure Activity Relationship (SAR) and to seek for more efficient radioprotector(s) other than edaravone. It was reported that a derivative with a pyridine ring as a substitute had much higher reactivity with hydroxyl radical than edaravone. However, the early processes of the reactions of edaravone derivatives are not fully understood and the quantitative data about their reaction rate have not been determined. In this study we investigated the reactions between some edaravone derivatives and hydroxyl radical and determined the rate constants of these reactions by pulse radiolysis technique. The rate constants were measured by three different methods. The first was direct measurement from the buildup kinetics of transient radicals. The second was competition method using carbonate ion as a competitor. The third was competitive measurement using DMPO, which is widely used spin-trapping agent for hydroxyl radical or hydrogen atom. The experimental results showed high reactivity of all derivatives investigated in this study. These reactions are near diffusion controlled. Moreover, the rate constants of derivatives with a pyridine ring by competition with DMPO were estimated twice as high as that by direct measurement. A possible interaction between the pyridine ring and DMPO is proposed.