Ligustrazine-vanillic acid derivatives had been reported to exhibit promising neuroprotective activities. In our continuous effort to develop new ligustrazine derivatives with neuroprotective effects, we attempted the synthesis of several ligustrazine-vanillic acid amide derivatives and screened their protective effect on the injured PC12 cells damaged by CoCl2. The results showed that most of the newly synthesized derivatives exhibited higher activity than ligustrazine, of which, compound VA-06 displayed the highest potency with EC50 values of 17.39 ± 1.34 μM. Structure-activity relationships were briefly discussed.Graphical abstractNew series of ligustrazine-vanillic acid amide derivatives were synthesized and evaluated for their protective effect on the injured PC12 cells damaged by CoCl2. VA-06 was found to be the most active one.
Keywords: Neuroprotective effect; PC12 cell; Synthesis; T-VA amide derivatives.