Reactivity of 9-aminoacridine drug quinacrine with glutathione limits its antiprion activity
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F17%3A00477495" target="_blank" >RIV/61388963:_____/17:00477495 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/17:10364151
Result on the web
<a href="http://dx.doi.org/10.1111/cbdd.12918" target="_blank" >http://dx.doi.org/10.1111/cbdd.12918</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1111/cbdd.12918" target="_blank" >10.1111/cbdd.12918</a>
Alternative languages
Result language
angličtina
Original language name
Reactivity of 9-aminoacridine drug quinacrine with glutathione limits its antiprion activity
Original language description
Quinacrine-the drug based on 9-aminoacridine-failed in clinical trials for prion diseases, whereas it was active in in vitro studies. We hypothesize that aromatic nucleophilic substitution at C9 could be contributing factor responsible for this failure because of the transfer of acridine moiety from quinacrine to abundant glutathione. Here, we described the semi-large-scale synthesis of the acridinylated glutathione and the consequences of its formation on biological and biophysical activities. The acridinylated glutathione is one order of magnitude weaker prion protein binder than the parent quinacrine. Moreover, according to log D-pH 7.4, the glutathione conjugate is two orders of magnitude more hydrophilic than quinacrine. Its higher hydrophilicity and higher dsDNA binding potency will significantly decrease its bioavailability in membrane-like environment. The glutathione deactivates quinacrine not only directly but also decreases its bioavailability. Furthermore, the conjugate can spontaneously decompose to practically insoluble acridone, which is precipitated out from the living systems.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10403 - Physical chemistry
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Chemical Biology & Drug Design
ISSN
1747-0277
e-ISSN
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Volume of the periodical
89
Issue of the periodical within the volume
6
Country of publishing house
GB - UNITED KINGDOM
Number of pages
11
Pages from-to
932-942
UT code for WoS article
000405100700011
EID of the result in the Scopus database
2-s2.0-85019199825