Inspired by the previously reported neuroprotective activity of hederacolchiside E (1), we synthesized hederacolchiside E for the first time along with eleven of its derivatives. The neuroprotective effects of these compounds were further evaluated against H₂O₂- and Aβ_1-42-induced injury using cell-based assays. The derivatives showed obvious differences in activity due to structural variations, and two of them exhibited better neuroprotective effects than 1 in the Aβ_1-42-induced injury model. Compound 7 was the most active derivative and had a relatively simple chemical structure. Moreover, 1 and 7 can significantly reduce the release of lactate dehydrogenase (LDH), level of intracellular reactive oxygen species (ROS) and extent of malondialdehyde (MDA) increase resulting from Aβ_1-42 treatment, which demonstrated that these kinds of compounds show neuroprotective effects in Alzheimer's disease (AD) models via modulating oxidative stress. Compound 7 could be used as promising lead for the development of a new type of neuroprotective agent against AD.

受先前报道的二十碳五烯苷E（1）的神经保护活性的启发，我们首次合成了二十碳五烯苷E及其11种衍生物。这些化合物的神经保护作用对h的进一步评价₂ ö ₂ -和A β _1-42使用基于细胞的测定诱导的损伤。这些衍生物显示出活性由于结构变化明显的差异，并且其中的两个表现出比更好的神经保护作用1在A β _1-42诱导的损伤模型。化合物7是活性最高的衍生物，并且具有相对简单的化学结构。此外，1和7可以显著降低乳酸脱氢酶（LDH），细胞内活性氧簇（ROS）和从A所得丙二醛（MDA）的增加程度的级别的释放β _1-42处理，这表明，这些种类的化合物显示在神经保护作用阿尔茨海默病（AD）通过调节氧化应激进行建模。化合物7可用作开发针对AD的新型神经保护剂的有希望的先导。