Synthesis and radical-scavenging activity of C-methylated fisetin analogues.

ABSTRACT

The radical-scavenging reaction of fisetin, a natural antioxidant found in strawberries, is known to proceed via hydrogen transfer to produce a fisetin radical intermediate. Thus, introduction of an electron-donating group into the fisetin molecule is expected to stabilize the radical, leading to enhanced radical-scavenging activity. In this study, fisetin derivatives in which methyl substituents were introduced at the ortho positions relative to the catechol hydroxyl groups were synthesized and their radical scavenging activities were evaluated and compared with that of the parent fisetin molecule. Among the methyl derivatives, 5'-methyl fisetin, in which the inherent planar structure of fisetin was retained, exhibited the strongest radical scavenging activity. Introduction of methyl substituents may be effective for the enhancement of various biological activities of antioxidants, particularly radical-scavenging activity.