摘要
为合成具有较强神经细胞氧化损伤保护作用的灯盏乙素苷元衍生物.以灯盏乙素苷元与N-取代氨甲基苯甲酸为原料,在偶联剂N,N'-二环己基碳酰亚胺(DCC)/4-N,N-二甲基吡啶(DMAP)的作用下制备了6种灯盏乙素苷元4'-N-取代氨甲基苯甲酸酯衍生物6a～6f,所合成的化合物均经过1H NMR,ESI-MS以及HRMS分析方法进行了结构表征,对化合物6a～6f进行了神经细胞氧化损伤保护活性与理化性质研究.结果表明:所合成的化合物均能显著降低过氧化氢作用PC12细胞后升高的乳酸脱氢酶(LDH)水平,其中6c与6e氧化损伤保护活性显著优于VE.初步构效关系研究发现:目标化合物结构中N-取代氨甲基苯甲酸酯的N原子参与形成1,4-双杂环时其产生较强的抗氧化活性.
To synthesize scutellarein derivatives with improved neuroprotective activity, six 4＇-N-substituted-aminomethyl-benzoate derivatives of scutellarein were prepared in the presence of N,N＇dicyclohexylcarbodiimide （DCC）/4-dimethylaminopyridine （DMAP） with scutellarein and N-substituted-amino- methyl-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 PC 12 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 ac- tivity than positive control VE with LDH release rate （36.83 ± 1.78）% and （36.69± 1.68）% at 20 umol·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.
出处
《有机化学》
SCIE
CAS
CSCD
北大核心
2011年第7期1043-1048,共6页
Chinese Journal of Organic Chemistry
基金
贵州省科技厅攻关(No.黔科合GY字[2008]3028)
贵州省中药现代化科技产业研究开发专项(No.黔科合社字[2010]5019)
贵州省科技厅科技计划(No.黔科合计工字[2009]4001)
贵阳市科技局计划(No.ZKZHTZ[2009]9-3-04)资助项目
