Study of a potential inhibitor of acetylcholinesterase using UV spectrophotometry, NMR spectroscopy and molecular modeling
| Autor: | Nello Ronzani, Isabelle Correia, Nicole Platzer, Jean-Claude Beloeil, Bich-Thuy Doan |
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| Přispěvatelé: | Service de Biochimie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC) |
| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
[PHYS]Physics [physics]
Molecular model 010405 organic chemistry medicine.drug_class Stereochemistry [CHIM.ORGA]Chemical Sciences/Organic chemistry Organic Chemistry Nuclear magnetic resonance spectroscopy 010402 general chemistry 01 natural sciences Acetylcholinesterase 0104 chemical sciences Hydrophobic effect chemistry.chemical_compound chemistry Acetylcholinesterase inhibitor Docking (molecular) Acridine medicine Pyridinium Physical and Theoretical Chemistry ComputingMilieux_MISCELLANEOUS |
| Zdroj: | Journal of Physical Organic Chemistry Journal of Physical Organic Chemistry, Wiley, 2006, 19 (2), pp.148-156. ⟨10.1002/poc.1000⟩ Journal of Physical Organic Chemistry, Wiley, 2006, 19(2), pp.148-156 |
| ISSN: | 0894-3230 1099-1395 |
| DOI: | 10.1002/poc.1000⟩ |
| Popis: | 1-[6-(Acridine-9-carbonyloxy)hexyl]pyridinium chloride (1) was synthesized and studied as a potential inhibitor of acetylcholinesterase (AChE), which is frequently involved in Alzheimer's disease. UV spectrophotometry showed that 1 is a reversible and competitive inhibitor of AChE (Ki ≈ 2 × 10−7 M). NMR (TrNOESY) showed that 1, bonded to AChE, maintains an extended form that allows hydrophobic interactions to occur between the aliphatic chain and the deep and narrow gorge of AchE and favors interactions between the acridine group and the catalytic and anionic subsites situated at the bottom of the gorge, and also between the pyridinium ring and the peripheral site. A more detailed picture of the structure of the complex was obtained by combining NMR structural data and molecular modeling (docking, dynamics simulation and energy calculations). Copyright © 2006 John Wiley & Sons, Ltd. |
| Databáze: | OpenAIRE |
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