Pharmacophore-based virtual screening of catechol-o-methyltransferase (COMT) inhibitors to combat Alzheimer’s disease

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388955%3A_____%2F18%3A00484458" target="_blank" >RIV/61388955:_____/18:00484458 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1080/07391102.2017.1404931" target="_blank" >http://dx.doi.org/10.1080/07391102.2017.1404931</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1080/07391102.2017.1404931" target="_blank" >10.1080/07391102.2017.1404931</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Pharmacophore-based virtual screening of catechol-o-methyltransferase (COMT) inhibitors to combat Alzheimer’s disease

Popis výsledku v původním jazyce

Alzheimer’s disease (AD) is one of the most significant neurodegenerative disorders and its symptoms mostly appear innaged people. Catechol-o-methyltransferase (COMT) is one of the known target enzymes responsible for AD. With thenuse of 23 known inhibitors of COMT, a query has been generated and validated by screening against the database ofn1500 decoys to obtain the GH score and enrichment value. The crucial features of the known inhibitors were evaluatednby the online ZINC Pharmer to identify new leads from a ZINC database. Five hundred hits were retrieved from ZINCnPharmer and by ADMET (absorption, distribution, metabolism, excretion, and toxicity) filtering by using FAF-Drug-3nand 36 molecules were considered for molecular docking. From the COMT inhibitors, opicapone, fenoldopam, and quercetinnwere selected, while ZINC63625100_413 ZINC39411941_412, ZINC63234426_254, ZINC63637968_451, andnZINC64019452_303 were chosen for the molecular dynamics simulation analysis having high binding affinity and structuralnrecognition. This study identified the potential COMT inhibitors through pharmacophore-based inhibitor screeningnleading to a more complete understanding of molecular-level interactions.

Název v anglickém jazyce

Pharmacophore-based virtual screening of catechol-o-methyltransferase (COMT) inhibitors to combat Alzheimer’s disease

Popis výsledku anglicky

Alzheimer’s disease (AD) is one of the most significant neurodegenerative disorders and its symptoms mostly appear innaged people. Catechol-o-methyltransferase (COMT) is one of the known target enzymes responsible for AD. With thenuse of 23 known inhibitors of COMT, a query has been generated and validated by screening against the database ofn1500 decoys to obtain the GH score and enrichment value. The crucial features of the known inhibitors were evaluatednby the online ZINC Pharmer to identify new leads from a ZINC database. Five hundred hits were retrieved from ZINCnPharmer and by ADMET (absorption, distribution, metabolism, excretion, and toxicity) filtering by using FAF-Drug-3nand 36 molecules were considered for molecular docking. From the COMT inhibitors, opicapone, fenoldopam, and quercetinnwere selected, while ZINC63625100_413 ZINC39411941_412, ZINC63234426_254, ZINC63637968_451, andnZINC64019452_303 were chosen for the molecular dynamics simulation analysis having high binding affinity and structuralnrecognition. This study identified the potential COMT inhibitors through pharmacophore-based inhibitor screeningnleading to a more complete understanding of molecular-level interactions.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

Journal of Biomolecular Structure & Dynamics

ISSN

0739-1102

e-ISSN

—

Svazek periodika

36

Číslo periodika v rámci svazku

15

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

20

Strana od-do

3938-3957

Kód UT WoS článku

000455813900006

EID výsledku v databázi Scopus

2-s2.0-85039160483