Parameters for Irreversible Inactivation of Monoamine Oxidase
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388955%3A_____%2F20%3A00541318" target="_blank" >RIV/61388955:_____/20:00541318 - isvavai.cz</a>
Result on the web
<a href="http://hdl.handle.net/11104/0318893" target="_blank" >http://hdl.handle.net/11104/0318893</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3390/molecules25245908" target="_blank" >10.3390/molecules25245908</a>
Alternative languages
Result language
angličtina
Original language name
Parameters for Irreversible Inactivation of Monoamine Oxidase
Original language description
The irreversible inhibitors of monoamine oxidases (MAO) slow neurotransmitter metabolism in depression and neurodegenerative diseases. After oxidation by MAO, hydrazines, cyclopropylamines and propargylamines form a covalent adduct with the flavin cofactor. To assist the design of new compounds to combat neurodegeneration, we have updated the kinetic parameters defining the interaction of these established drugs with human MAO-A and MAO-B and analyzed the required features. The K-i values for binding to MAO-A and molecular models show that selectivity is determined by the initial reversible binding. Common to all the irreversible inhibitor classes, the non-covalent 3D-chemical interactions depend on a H-bond donor and hydrophobic-aromatic features within 5.7 angstroms apart and an ionizable amine. Increasing hydrophobic interactions with the aromatic cage through aryl halogenation is important for stabilizing ligands in the binding site for transformation. Good and poor inactivators were investigated using visible spectroscopy and molecular dynamics. The initial binding, close and correctly oriented to the FAD, is important for the oxidation, specifically at the carbon adjacent to the propargyl group. The molecular dynamics study also provides evidence that retention of the allenyl imine product oriented towards FADH(-) influences the formation of the covalent adduct essential for effective inactivation of MAO.
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
—
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Molecules
ISSN
1420-3049
e-ISSN
1420-3049
Volume of the periodical
25
Issue of the periodical within the volume
24
Country of publishing house
CH - SWITZERLAND
Number of pages
25
Pages from-to
5908
UT code for WoS article
000603179700001
EID of the result in the Scopus database
2-s2.0-85098534664