Synthesis, biological evaluation and structure-activity relationship studies of hederacolchiside E and its derivatives as potential anti-Alzheimer agents

Abstract 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 H 2 O 2 - and A β 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 β 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 β 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.