Novel Inhibitors of Acetyl- and Butyrylcholinesterase Derived from Benzohydrazides: Synthesis, Evaluation and Docking Study
The result's identifiers
Result code in 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>
Alternative codes found
RIV/00216275:25310/23:39920495
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
Novel Inhibitors of Acetyl- and Butyrylcholinesterase Derived from Benzohydrazides: Synthesis, Evaluation and Docking Study
Original language description
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'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.
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
30104 - Pharmacology and pharmacy
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
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Pharmaceuticals
ISSN
1424-8247
e-ISSN
1424-8247
Volume of the periodical
16
Issue of the periodical within the volume
2
Country of publishing house
CH - SWITZERLAND
Number of pages
20
Pages from-to
172
UT code for WoS article
000940955800001
EID of the result in the Scopus database
2-s2.0-85148941241