nNOS PDZ抑制剂的合成及其神经保护作用研究

目的:合成nNOS PDZ抑制剂并评价其神经保护作用?方法:根据nNOS PDZ结构域配体结合部位多碱性中心的结构特点设计并合成多系列双羧酸及其酯类化合物,用谷氨酸诱导的神经元细胞乳酸脱氢酶释放模型评价化合物的神经保护作用?结果:合成了18个目标化合物,其中N-(2-甲氧羰基乙酰基)-D-缬氨酸甲酯 (1)?N-(2-羧基乙酰基)-D-缬氨酸甲酯(2)?N-(2-甲氧羰基乙酰基)-L-缬氨酸甲酯(7)?N-(2-羧基乙酰基)-L-缬氨酸(9)显示较强的神经保护作用?结论:nNOS PDZ结构域抑制剂具有神经保护作用?

Synthesis and neuroprotective effect of nNOS PDZ structural domain inhibitors

Objective:To synthesize nNOS PDZ structural domain inhibitors and evaluate their neuroprotective effects. Methods:Multiple-series of dicarboxylic acids and their ester compounds were designed and synthesized based on the structure characteristic of multi-basic groups of the nNOS PDZ ligand binding domain. The neuroprotective effects of the compounds were evaluated by glutamate-induced lactate dehydrogenase (LDH) release model of neurons. Results:Eighteen target compounds were synthesized including N-(2-methoxycarbonylacetyl)-D-valine methyl ester(1),N-(2-carboxylacetyl)-D-valine methyl ester(2),N-(2-methoxycarbony-lacetyl)-L-valine methyl ester(7),N-(2-carboxylacetyl)-L-valine(9) showed potent neuroprotective effect. Conclusion:nNOS PDZ structural domain inhibitors are neuroprotective.