To synthesize scutellarein derivatives with improved neuroprotective activity, six 4-N-substi- tuted-aminomethyl-benzoate derivatives of scutellarein were prepared in the presence of N,N-dicyclo- hexylcarbodiimide (DCC)/4-dimethylaminopyridine (DMAP) with scutellarein and N-substituted-aminomethyl-benzoic acid as starting materials. The structures of the compounds 6a～6f were established by ¹H NMR, ESI-MS and HRMS techniques. The synthesized compounds were assayed by their physicochemical properties and in vitro anti-oxidative activity against H₂O₂ induced oxidative damage in PC12 cells. The results showed that all the compounds had potent anti-oxidative activity by reducing lactate dehydrogenase (LDH) level in concentration-dependent manner, compounds 6c and 6e have more potent anti-oxidative activity than positive control V_E with LDH release rate (36.83±1.78)% and (36.69±1.68)% at 20 μmol•L^－1 concentration. Primary structure-activity relationship revealed that compounds with N atom of (aminomethyl)benzoic acid involved in the formation of 1,4-bis-heterocyclic would have more potent anti-oxidative activity.

Key words: scutellarein, PC12 cells, anti-oxidative activity, aminomethyl-benzoic acid