Continental and Antarctic Lichens: isolation, identification andmolecularmodeling of the depside tenuiorin fromthe Antarctic lichen Umbilicaria antarctica as tau protein inhibitor

Alzheimer s disease (AD) is the most common form of dementia involv- ing 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 neurodege- nerative disorder...

Full description

Bibliographic Details
Published in:Natural Product Research
Main Authors: Salgado, Francisco, Caballero, Julio, Vargas, Reinaldo, Cornejo, Alberto, Areche-Medina, Carlos Alberto
Format: Article in Journal/Newspaper
Language:unknown
Subjects:
Online Access:http://hdl.handle.net/10533/236463
https://doi.org/10.1080/14786419.2018.1492576
Description
Summary:Alzheimer s disease (AD) is the most common form of dementia involv- ing 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 neurodege- nerative disorders named as tauopathies. Here, we have isolated seven- teen 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 sug- gested that tenuiorin forms both hydrogen bonds with lysine and glu- tamine side chains and forms several hydrophobic interactions with valine and lysine from306VQIVYK311motif.