Synthesis, biological evaluation and structure-activity relationship studies of hederacolchiside E and its derivatives as potential anti-Alzheimer agents
| Autor: | Zhi-peng Wang, Libo Zou, Hui-ning Li, Yang Liu, Zuo-Peng Zhang, Zhan-Fang Fan, Jing-zheng Hao, Maosheng Cheng, Fengran Li |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cell Survival Chemical structure Cell Pharmacology medicine.disease_cause 01 natural sciences Neuroprotection PC12 Cells 03 medical and health sciences chemistry.chemical_compound Structure-Activity Relationship Alzheimer Disease Lactate dehydrogenase Drug Discovery medicine Structure–activity relationship Animals Cells Cultured Amyloid beta-Peptides Dose-Response Relationship Drug L-Lactate Dehydrogenase Molecular Structure 010405 organic chemistry Chemistry Organic Chemistry General Medicine Hydrogen Peroxide Saponins Malondialdehyde Peptide Fragments 0104 chemical sciences Rats 030104 developmental biology medicine.anatomical_structure Neuroprotective Agents Hederacolchiside-E Reactive Oxygen Species Oxidative stress |
| Zdroj: | European journal of medicinal chemistry. 143 |
| ISSN: | 1768-3254 |
| Popis: | 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 Aβ1-42-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 Aβ1-42-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 Aβ1-42 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. |
| Databáze: | OpenAIRE |
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