Synthesis, biological evaluation and structure-activity relationship studies of hederacolchiside E and its derivatives as potential anti-Alzheimer agents
Synthesis, biological evaluation and structure-activity relationship studies of hederacolchiside E and its derivatives as potential anti-Alzheimer agents
复制标题
常春藤苷E及其衍生物作为潜在抗阿尔茨海默病药物的合成、生物学评价及构效关系研究
DOI：
10.1016/j.ejmech.2017.11.040
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发表时间：
2018-01-01
影响因子：
6.7
通讯作者：
Cheng, Mao-sheng
中科院分区：
文献类型：
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作者：
Li, Hui-ning;Liu, Yang;Cheng, Mao-sheng
受先前报道的常春藤苷 E (1) 神经保护活性的启发，我们首次合成了常春藤苷 E 及其 11 种衍生物。使用基于细胞的测定进一步评估了这些化合物对 H2O2 和 A beta(1-42) 诱导的损伤的神经保护作用。由于结构变异，这些衍生物表现出明显的活性差异，其中两种衍生物在A beta(1-42)诱导的损伤模型中表现出比1种更好的神经保护作用。化合物7是最活跃的衍生物并且具有相对简单的化学结构。此外，1和7可以显着减少Aβ(1-42)治疗引起的乳酸脱氢酶(LDH)释放、细胞内活性氧(ROS)水平和丙二醛(MDA)增加程度，这表明这些化合物通过调节氧化应激在阿尔茨海默病(AD)模型中显示出神经保护作用。化合物 7 可作为开发新型抗 AD 神经保护剂的先导化合物。 (C) 2017 Elsevier Masson SAS。版权所有。
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 A beta(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 A beta(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 A beta(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. (C) 2017 Elsevier Masson SAS. All rights reserved.