Novel Inhibitors of Acetyl- and Butyrylcholinesterase Derived from Benzohydrazides: Synthesis, Evaluation and Docking Study

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F23%3A10472127" target="_blank" >RIV/00216208:11160/23:10472127 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216275:25310/23:39920495

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=pekGtGY_Dj" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=pekGtGY_Dj</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/ph16020172" target="_blank" >10.3390/ph16020172</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Novel Inhibitors of Acetyl- and Butyrylcholinesterase Derived from Benzohydrazides: Synthesis, Evaluation and Docking Study

Popis výsledku v původním jazyce

On the basis of previous reports, novel 2-benzoylhydrazine-1-carboxamides were designed as potential inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Inhibitors of these enzymes have many clinical applications. 2-(Substituted benzoyl)hydrazine-1-carboxamides decorated with N-methyl or tridecyl were prepared with three methods from commercially available or self-prepared hydrazides and isocyanates. For methyl derivatives, N-succinimidyl N-methylcarbamate was used or methyl isocyanate was prepared via Curtius rearrangement. Tridecyl isocyanate was synthesized again via Curtius rearrangement or from triphosgene and tridecylamine. The compounds were evaluated for the inhibition of AChE and BChE using Ellman&apos;s spectrophotometric method. Most of the derivatives showed the dual inhibition of both enzymes with IC(50) values of 44-100 mu M for AChE and from 22 mu M for BChE. In general, the carboxamides inhibited AChE more strongly. A large number of the compounds showed better or quite comparable inhibition of cholinesterases in vitro than that of the drug rivastigmine. Molecular docking was performed to investigate the possible conformation of the compounds and their interactions with target enzymes. In both AChE and BChE, the compounds occupied the enzyme active cavity, and, especially in the case of BChE, the compounds were placed in close proximity to the catalytic triad.

Název v anglickém jazyce

Novel Inhibitors of Acetyl- and Butyrylcholinesterase Derived from Benzohydrazides: Synthesis, Evaluation and Docking Study

Popis výsledku anglicky

On the basis of previous reports, novel 2-benzoylhydrazine-1-carboxamides were designed as potential inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Inhibitors of these enzymes have many clinical applications. 2-(Substituted benzoyl)hydrazine-1-carboxamides decorated with N-methyl or tridecyl were prepared with three methods from commercially available or self-prepared hydrazides and isocyanates. For methyl derivatives, N-succinimidyl N-methylcarbamate was used or methyl isocyanate was prepared via Curtius rearrangement. Tridecyl isocyanate was synthesized again via Curtius rearrangement or from triphosgene and tridecylamine. The compounds were evaluated for the inhibition of AChE and BChE using Ellman&apos;s spectrophotometric method. Most of the derivatives showed the dual inhibition of both enzymes with IC(50) values of 44-100 mu M for AChE and from 22 mu M for BChE. In general, the carboxamides inhibited AChE more strongly. A large number of the compounds showed better or quite comparable inhibition of cholinesterases in vitro than that of the drug rivastigmine. Molecular docking was performed to investigate the possible conformation of the compounds and their interactions with target enzymes. In both AChE and BChE, the compounds occupied the enzyme active cavity, and, especially in the case of BChE, the compounds were placed in close proximity to the catalytic triad.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2023

Kód důvěrnosti údajů

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

Název periodika

Pharmaceuticals

ISSN

1424-8247

e-ISSN

1424-8247

Svazek periodika

16

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

20

Strana od-do

172

Kód UT WoS článku

000940955800001

EID výsledku v databázi Scopus

2-s2.0-85148941241