Effects of Novel Tacrine Derivatives on Mitochondrial Energy Metabolism and Monoamine Oxidase Activity-In Vitro Study
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F21%3A10425683" target="_blank" >RIV/00216208:11110/21:10425683 - isvavai.cz</a>
Alternative codes found
RIV/60162694:G44__/21:00556321 RIV/00179906:_____/21:10425683
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=~uFJ6xC.fc" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=~uFJ6xC.fc</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1007/s12035-020-02172-1" target="_blank" >10.1007/s12035-020-02172-1</a>
Alternative languages
Result language
angličtina
Original language name
Effects of Novel Tacrine Derivatives on Mitochondrial Energy Metabolism and Monoamine Oxidase Activity-In Vitro Study
Original language description
The trends of novel AD therapeutics are focused on multitarget-directed ligands (MTDLs), which combine cholinesterase inhibition with additional biological properties such as antioxidant properties to positively affect neuronal energy metabolism as well as mitochondrial function. We examined the in vitro effects of 10 novel MTDLs on the activities of mitochondrial enzymes (electron transport chain complexes and citrate synthase), mitochondrial respiration, and monoamine oxidase isoform (MAO-A and MAO-B) activity. The drug-induced effects of 7-MEOTA-adamantylamine heterodimers (K1011, K1013, K1018, K1020, and K1022) and tacrine/7-MEOTA/6-chlorotacrine-trolox heterodimers (K1046, K1053, K1056, K1060, and K1065) were measured in pig brain mitochondria. Most of the substances inhibited complex I- and complex II-linked respiration at high concentrations; K1046, K1053, K1056, and K1060 resulted in the least inhibition of mitochondrial respiration. Citrate synthase activity was not significantly inhibited by the tested substances; the least inhibition of complex I was observed for compounds K1060 and K1053, while both complex II/III and complex IV activity were markedly inhibited by K1011 and K1018. MAO-A was fully inhibited by K1018 and K1065, and MAO-B was fully inhibited by K1053 and K1065; the other tested drugs were partial inhibitors of both MAO-A and MAO-B. The tacrine/7-MEOTA/6-chlorotacrine-trolox heterodimers K1046, K1053, and K1060 seem to be the most suitable molecules for subsequent in vivo studies. These compounds had balanced inhibitory effects on mitochondrial respiration, with low complex I and complex II/III inhibition and full or partial inhibition of MAO-B activity.
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
<a href="/en/project/GJ17-07585Y" target="_blank" >GJ17-07585Y: Effect of cholinesterase inhibitors on monoaminergic system and energy metabolism</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
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
Molecular Neurobiology
ISSN
0893-7648
e-ISSN
—
Volume of the periodical
58
Issue of the periodical within the volume
3
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
1102-1113
UT code for WoS article
000580961100001
EID of the result in the Scopus database
2-s2.0-85092898388