Faculty of Chemistry Repository - Cherry
University of Belgrade - Faculty of Chemistry
    • English
    • Српски
    • Српски (Serbia)
  • English 
    • English
    • Serbian (Cyrillic)
    • Serbian (Latin)
  • Login
View Item 
  •   Cherry
  • Hemijski fakultet
  • Publikacije
  • View Item
  •   Cherry
  • Hemijski fakultet
  • Publikacije
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Structural modifications of 4-aryl-4-oxo-2-aminylbutanamides and their acetyl- and butyrylcholinesterase inhibitory activity. Investigation of AChE-ligand interactions by docking calculations and molecular dynamics simulations

Authorized Users Only
2014
Authors
Vitorović-Todorović, Maja D.
Koukoulitsa, Catherine
Juranić, Ivan O.
Mandić, Ljuba M.
Drakulić, Branko J.
Article (Accepted Version)
Metadata
Show full item record
Abstract
Congeneric set of thirty-eight 4-aryl-4-oxo-2-(N-aryl/cycloalkyl)butanamides has been designed, synthesized and evaluated for acetyl- and butyrylcholinesterase inhibitory activity. Structural variations included cycloalkylamino group attached to C2 position of butanoyl moiety, and variation of amido moiety of molecules. Twelve compounds, mostly piperidino and imidazolo derivatives, inhibited AChE in low micromolar range, and were inactive toward BChE. Several N-methylpiperazino derivatives showed inhibition of BChE in low micromolar or submicromolar concentrations, and were inactive toward AChE. Therefore, the nature of the cycloalkylamino moiety governs the AChE/BChE selectivity profile of compounds. The most active AChE inhibitor showed mixed-type inhibition modality, indicating its binding to free enzyme and to enzyme-substrate complex. Thorough docking calculations of the seven most potent AChE inhibitors from the set, showed that the hydrogen bond can be formed between amide -NH- ...moiety of compounds and -OH group of Tyr 124. The 10 ns unconstrained molecular dynamic simulation of the AChE- compound 18 complex shows that this interaction is the most persistent. This is, probably, the major anchoring point for the binding. (C) 2014 Elsevier Masson SAS. All rights reserved.

Keywords:
4-Aryl-4-oxo-2-aminylbutyramides / Anticholinesterase activity / Mixed type reversible inhibitors / Docking study / Molecular dynamics
Source:
European Journal of Medicinal Chemistry, 2014, 81, 158-175
Publisher:
  • Elsevier France-Editions Scientifiques Medicales Elsevier, Paris
Funding / projects:
  • Rational design and synthesis of biologically active and coordination compounds and functional materials, relevant for (bio)nanotechnology (RS-172035)
Note:
  • Supplementary material: http://cherry.chem.bg.ac.rs/handle/123456789/2906
  • This is the peer-reviewed version of the article: Vitorović-Todorović, M. D.; Koukoulitsa, C.; Juranić, I. O.; Mandić, L. M.; Drakulić, B. J. Structural Modifications of 4-Aryl-4-Oxo-2-Aminylbutanamides and Their Acetyl- and Butyrylcholinesterase Inhibitory Activity. Investigation of AChE-Ligand Interactions by Docking Calculations and Molecular Dynamics Simulations. European Journal of Medicinal Chemistry 2014, 81, 158–175. https://doi.org/10.1016/j.ejmech.2014.05.008

DOI: 10.1016/j.ejmech.2014.05.008

ISSN: 0223-5234

PubMed: 24836068

WoS: 000338598400015

Scopus: 2-s2.0-84900870587
[ Google Scholar ]
15
16
URI
https://cherry.chem.bg.ac.rs/handle/123456789/2907
Collections
  • Publikacije
Institution/Community
Hemijski fakultet
TY  - JOUR
AU  - Vitorović-Todorović, Maja D.
AU  - Koukoulitsa, Catherine
AU  - Juranić, Ivan O.
AU  - Mandić, Ljuba M.
AU  - Drakulić, Branko J.
PY  - 2014
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2907
AB  - Congeneric set of thirty-eight 4-aryl-4-oxo-2-(N-aryl/cycloalkyl)butanamides has been designed, synthesized and evaluated for acetyl- and butyrylcholinesterase inhibitory activity. Structural variations included cycloalkylamino group attached to C2 position of butanoyl moiety, and variation of amido moiety of molecules. Twelve compounds, mostly piperidino and imidazolo derivatives, inhibited AChE in low micromolar range, and were inactive toward BChE. Several N-methylpiperazino derivatives showed inhibition of BChE in low micromolar or submicromolar concentrations, and were inactive toward AChE. Therefore, the nature of the cycloalkylamino moiety governs the AChE/BChE selectivity profile of compounds. The most active AChE inhibitor showed mixed-type inhibition modality, indicating its binding to free enzyme and to enzyme-substrate complex. Thorough docking calculations of the seven most potent AChE inhibitors from the set, showed that the hydrogen bond can be formed between amide -NH- moiety of compounds and -OH group of Tyr 124. The 10 ns unconstrained molecular dynamic simulation of the AChE- compound 18 complex shows that this interaction is the most persistent. This is, probably, the major anchoring point for the binding. (C) 2014 Elsevier Masson SAS. All rights reserved.
PB  - Elsevier France-Editions Scientifiques Medicales Elsevier, Paris
T2  - European Journal of Medicinal Chemistry
T1  - Structural modifications of 4-aryl-4-oxo-2-aminylbutanamides and their acetyl- and butyrylcholinesterase inhibitory activity. Investigation of AChE-ligand interactions by docking calculations and molecular dynamics simulations
VL  - 81
SP  - 158
EP  - 175
DO  - 10.1016/j.ejmech.2014.05.008
UR  - Kon_2691
ER  - 
@article{
author = "Vitorović-Todorović, Maja D. and Koukoulitsa, Catherine and Juranić, Ivan O. and Mandić, Ljuba M. and Drakulić, Branko J.",
year = "2014",
abstract = "Congeneric set of thirty-eight 4-aryl-4-oxo-2-(N-aryl/cycloalkyl)butanamides has been designed, synthesized and evaluated for acetyl- and butyrylcholinesterase inhibitory activity. Structural variations included cycloalkylamino group attached to C2 position of butanoyl moiety, and variation of amido moiety of molecules. Twelve compounds, mostly piperidino and imidazolo derivatives, inhibited AChE in low micromolar range, and were inactive toward BChE. Several N-methylpiperazino derivatives showed inhibition of BChE in low micromolar or submicromolar concentrations, and were inactive toward AChE. Therefore, the nature of the cycloalkylamino moiety governs the AChE/BChE selectivity profile of compounds. The most active AChE inhibitor showed mixed-type inhibition modality, indicating its binding to free enzyme and to enzyme-substrate complex. Thorough docking calculations of the seven most potent AChE inhibitors from the set, showed that the hydrogen bond can be formed between amide -NH- moiety of compounds and -OH group of Tyr 124. The 10 ns unconstrained molecular dynamic simulation of the AChE- compound 18 complex shows that this interaction is the most persistent. This is, probably, the major anchoring point for the binding. (C) 2014 Elsevier Masson SAS. All rights reserved.",
publisher = "Elsevier France-Editions Scientifiques Medicales Elsevier, Paris",
journal = "European Journal of Medicinal Chemistry",
title = "Structural modifications of 4-aryl-4-oxo-2-aminylbutanamides and their acetyl- and butyrylcholinesterase inhibitory activity. Investigation of AChE-ligand interactions by docking calculations and molecular dynamics simulations",
volume = "81",
pages = "158-175",
doi = "10.1016/j.ejmech.2014.05.008",
url = "Kon_2691"
}
Vitorović-Todorović, M. D., Koukoulitsa, C., Juranić, I. O., Mandić, L. M.,& Drakulić, B. J.. (2014). Structural modifications of 4-aryl-4-oxo-2-aminylbutanamides and their acetyl- and butyrylcholinesterase inhibitory activity. Investigation of AChE-ligand interactions by docking calculations and molecular dynamics simulations. in European Journal of Medicinal Chemistry
Elsevier France-Editions Scientifiques Medicales Elsevier, Paris., 81, 158-175.
https://doi.org/10.1016/j.ejmech.2014.05.008
Kon_2691
Vitorović-Todorović MD, Koukoulitsa C, Juranić IO, Mandić LM, Drakulić BJ. Structural modifications of 4-aryl-4-oxo-2-aminylbutanamides and their acetyl- and butyrylcholinesterase inhibitory activity. Investigation of AChE-ligand interactions by docking calculations and molecular dynamics simulations. in European Journal of Medicinal Chemistry. 2014;81:158-175.
doi:10.1016/j.ejmech.2014.05.008
Kon_2691 .
Vitorović-Todorović, Maja D., Koukoulitsa, Catherine, Juranić, Ivan O., Mandić, Ljuba M., Drakulić, Branko J., "Structural modifications of 4-aryl-4-oxo-2-aminylbutanamides and their acetyl- and butyrylcholinesterase inhibitory activity. Investigation of AChE-ligand interactions by docking calculations and molecular dynamics simulations" in European Journal of Medicinal Chemistry, 81 (2014):158-175,
https://doi.org/10.1016/j.ejmech.2014.05.008 .,
Kon_2691 .

DSpace software copyright © 2002-2015  DuraSpace
About CHERRY - CHEmistry RepositoRY | Send Feedback

re3dataOpenAIRERCUB
 

 

All of DSpaceInstitutions/communitiesAuthorsTitlesSubjectsThis institutionAuthorsTitlesSubjects

Statistics

View Usage Statistics

DSpace software copyright © 2002-2015  DuraSpace
About CHERRY - CHEmistry RepositoRY | Send Feedback

re3dataOpenAIRERCUB