三苯基吡唑甲酮类化合物的合成及对6-OHDA 损伤的SH-SY5Y 细胞的保护作用

Synthesis of triphenylpyrazole ketone compounds and their protective action against 6-OHDA induced injury in SH-SY5Y cells

目的设计合成系列三苯基吡唑甲酮类化合物,测定其对6-羟基多巴胺(6-OHDA)损伤的SH-SY5Y细胞的保护作用,并初步探讨其构效关系。方法以2,5-二甲氧基苯乙酮为起始原料,经过Claisen-Schmidt反应和亲核加成合成目标化合物。采用CCK-8法考察了目标化合物对6-OHDA损伤的SH-SY5Y细胞的保护作用。结果与结论合成了8个未见文献报道的新化合物,其结构均经MS、1H-NMR、13C-NMR谱确证。体外活性筛选结果表明,化合物4c、4d、5c、5d具有较好的细胞保护作用,其EC50值为1.1~9.6μmol·L-1,与阳性对照雷沙吉兰相当(EC50=1.6μmol·L-1)。

A series of triphenylpyrazolone compounds were designed and synthesized,and their protective action against 6-OHDA induced SH-SY5 Y cell injury was evaluated.In this study,eight new target compounds were synthesized through Claisen-Schmidt reaction and nucleophilic addition with 2,5-dimethoxyacetophenone as the starting material,their structures were analyzed by MS,1H-NMR and 13C-NMR spectra.Preliminary results showed that the target compounds 4 c,4 d,5 c,and 5 d exhibited the excellent activity with the EC50values 1.1-9.6μmol·L-1,which were equivalent to the positive control rasagiline(EC50=1.6μmol·L-1).