Continental and Antarctic Lichens: isolation, identification and molecular modeling of the depside tenuiorin from the Antarctic lichen Umbilicaria antarctica as tau protein inhibitor
Alzheimer s disease (AD) is the most common form of dementia involving Ab and tau protein. So far, AD cure remains elusive, but considering that AD progresses throughout tau pathology, which turns tau protein an appropriate target, besides tau is also included in other neurodegenerative disorders na...
| Published in: | Natural Product Research |
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| Main Authors: | , , , , |
| Format: | Article in Journal/Newspaper |
| Language: | English |
| Published: |
Taylor & Francis
2020
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| Subjects: | |
| Online Access: | https://doi.org/10.1080/14786419.2018.1492576 https://repositorio.uchile.cl/handle/2250/174423 |
| Summary: | Alzheimer s disease (AD) is the most common form of dementia involving Ab and tau protein. So far, AD cure remains elusive, but considering that AD progresses throughout tau pathology, which turns tau protein an appropriate target, besides tau is also included in other neurodegenerative disorders named as tauopathies. Here, we have isolated seventeen compounds belonging to six lichens species. Due to scarce of spectroscopic data of the compound 5,7-dihydroxy-6-methylphthalide, we explained their structural elucidation based on NMR data. In this study, we show that only tenuiorin from Umbilicaria antarctica inhibited 50% of tau 4R at 100mM. Then, we shown that molecular interactions of tenuiorin with the steric zipper model of the hexapeptide 306VQIVYK311 were studied by docking calculations and the results suggested that tenuiorin forms both hydrogen bonds with lysine and glutamine side chains and forms several hydrophobic interactions with valine and lysine from 306VQIVYK311 motif. Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) CONICYT FONDECYT 1150745 INACH RT 13-13 MT 03-14 Fondo Nacional de Desarrollo Cientifico and Tecnologico |
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