In Vitro and In Silico Acetylcholinesterase Inhibitory Activity of Thalictricavine and Canadine and Their Predicted Penetration across the Blood-Brain Barrier

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F19%3A00536709" target="_blank" >RIV/60162694:G44__/19:00536709 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11160/19:10400166 RIV/00216275:25310/19:39914658 RIV/00179906:_____/19:10400166

Result on the web

<a href="https://www.mdpi.com/1420-3049/24/7/1340" target="_blank" >https://www.mdpi.com/1420-3049/24/7/1340</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/molecules24071340" target="_blank" >10.3390/molecules24071340</a>

Result language

angličtina

Original language name

In Vitro and In Silico Acetylcholinesterase Inhibitory Activity of Thalictricavine and Canadine and Their Predicted Penetration across the Blood-Brain Barrier

Original language description

In recent studies, several alkaloids acting as cholinesterase inhibitors were isolated from Corydalis cava (Papaveraceae). Inhibitory activities of (+)-thalictricavine (1) and (+)-canadine (2) on human acetylcholinesterase (hAChE) and butyrylcholinesterase (hBChE) were evaluated with the Ellman's spectrophotometric method. Molecular modeling was used to inspect the binding mode of compounds into the active site pocket of hAChE. The possible permeability of 1 and 2 through the blood-brain barrier (BBB) was predicted by the parallel artificial permeation assay (PAMPA) and logBB calculation. In vitro, 1 and 2 were found to be selective hAChE inhibitors with IC50 values of 0.38 +/- 0.05 mu M and 0.70 +/- 0.07 mu M, respectively, but against hBChE were considered inactive (IC50 values > 100 mu M). Furthermore, both alkaloids demonstrated a competitive-type pattern of hAChE inhibition and bind, most probably, in the same AChE sub-site as its substrate. In silico docking experiments allowed us to confirm their binding poses into the active center of hAChE. Based on the PAMPA and logBB calculation, 2 is potentially centrally active, but for 1 BBB crossing is limited. In conclusion, 1 and 2 appear as potential lead compounds for the treatment of Alzheimer's disease.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2019

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Molecules

ISSN

1420-3049

e-ISSN

—

Volume of the periodical

24

Issue of the periodical within the volume

7

Country of publishing house

CH - SWITZERLAND

Number of pages

11

Pages from-to

1340

UT code for WoS article

000464959900006

EID of the result in the Scopus database

2-s2.0-85064092214