Discovery of sustainable drugs for Alzheimer's disease: cardanol-derived cholinesterase inhibitors with antioxidant and anti-amyloid properties
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F21%3A10430048" target="_blank" >RIV/00179906:_____/21:10430048 - isvavai.cz</a>
Alternative codes found
RIV/60162694:G44__/21:00556966
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=x.oWe75Lcf" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=x.oWe75Lcf</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1039/d1md00046b" target="_blank" >10.1039/d1md00046b</a>
Alternative languages
Result language
angličtina
Original language name
Discovery of sustainable drugs for Alzheimer's disease: cardanol-derived cholinesterase inhibitors with antioxidant and anti-amyloid properties
Original language description
As part of our efforts to develop sustainable drugs for Alzheimer's disease (AD), we have been focusing on the inexpensive and largely available cashew nut shell liquid (CNSL) as a starting material for the identification of new acetylcholinesterase (AChE) inhibitors. Herein, we decided to investigate whether cardanol, a phenolic CNSL component, could serve as a scaffold for improved compounds with concomitant anti-amyloid and antioxidant activities. Ten new derivatives, carrying the intact phenolic function and an aminomethyl functionality, were synthesized and first tested for their inhibitory potencies towards AChE and butyrylcholinesterase (BChE). 5 and 11 were found to inhibit human BChE at a single-digit micromolar concentration. Transmission electron microscopy revealed the potential of five derivatives to modulate A beta aggregation, including 5 and 11. In HORAC assays, 5 and 11 performed similarly to standard antioxidant ferulic acid as hydroxyl scavenging agents. Furthermore, in in vitro studies in neuronal cell cultures, 5 and 11 were found to effectively inhibit reactive oxygen species production at a 10 mu M concentration. They also showed a favorable initial ADME/Tox profile. Overall, these results suggest that CNSL is a promising raw material for the development of potential disease-modifying treatments for AD.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
30104 - Pharmacology and pharmacy
Result continuities
Project
—
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
RSC Medicinal Chemistry [online
ISSN
2632-8682
e-ISSN
—
Volume of the periodical
12
Issue of the periodical within the volume
7
Country of publishing house
GB - UNITED KINGDOM
Number of pages
10
Pages from-to
1154-1163
UT code for WoS article
000647143300001
EID of the result in the Scopus database
2-s2.0-85111158492