New developments in redox chemical delivery systems by means of 1,4-dihydroquinoline-based targetor: application to galantamine delivery to the brain.
The therapeutic efficiency of palliative treatments of AD, mostly based on acetylcholinesterase (AChE) inhibitors, is marred by serious adverse effects due to peripheral activity of these AChE inhibitors. In the literature, a redox-based chemical delivery system (CDS) has been developed to enhance drugs distribution to the brain while reducing peripheral side effects. Herein, we disclose two new synthetic strategies for the preparation of 1,4-dihydroquinoline/quinolinium salt redox-based systems particularly well designed for brain delivery of drugs sensitive to alkylation reactions. These strategies have been applied in the present case to the AChE inhibitor galantamine with the aim of alleviating adverse effects observed with cholinergic AD treatment. The first strategy is based on an intramolecular alkylation reaction as key step, whilst the second strategy relies on a useful coupling between galantamine and quinolinium salt key intermediate. In the course of this work, polymer-supported reagents and a solid-phase synthesis approach revealed to be highly helpful to develop this redox-based galantamine CDS.
Normandie Univ, COBRA, UMR 6014 et FR 3038, Univ Rouen, INSA Rouen, CNRS, IRCOF, 1 Rue Tesnière, 76821 Mont Saint Aignan Cedex, France.
Mihaela-Liliana
ML
Ţînţaş
Normandie Univ, COBRA, UMR 6014 et FR 3038, Univ Rouen, INSA Rouen, CNRS, IRCOF, 1 Rue Tesnière, 76821 Mont Saint Aignan Cedex, France.
Lénaïg
L
Foucout
Normandie Univ, COBRA, UMR 6014 et FR 3038, Univ Rouen, INSA Rouen, CNRS, IRCOF, 1 Rue Tesnière, 76821 Mont Saint Aignan Cedex, France.
Sylvain
S
Petit
Normandie Univ, COBRA, UMR 6014 et FR 3038, Univ Rouen, INSA Rouen, CNRS, IRCOF, 1 Rue Tesnière, 76821 Mont Saint Aignan Cedex, France.
Sylvain
S
Oudeyer
CEA, DSV/I2BM, LDM-TEP Group, GIP Cyceron, Bd Henri Becquerel, BP 5229, 14074 Caen Cedex, France; Université de Caen Basse-Normandie, Caen, France; CNRS, UMR ISTCT 6301, LDM-TEP Group, GIP Cyceron, Caen, France.
Fabienne
F
Gourand
CEA, DSV/I2BM, LDM-TEP Group, GIP Cyceron, Bd Henri Becquerel, BP 5229, 14074 Caen Cedex, France; Université de Caen Basse-Normandie, Caen, France; CNRS, UMR ISTCT 6301, LDM-TEP Group, GIP Cyceron, Caen, France.
Louisa
L
Barré
Normandie Univ, COBRA, UMR 6014 et FR 3038, Univ Rouen, INSA Rouen, CNRS, IRCOF, 1 Rue Tesnière, 76821 Mont Saint Aignan Cedex, France. Electronic address: cyril.papamicael@insa-rouen.fr.
Cyril
C
Papamicaël
Normandie Univ, COBRA, UMR 6014 et FR 3038, Univ Rouen, INSA Rouen, CNRS, IRCOF, 1 Rue Tesnière, 76821 Mont Saint Aignan Cedex, France. Electronic address: vincent.levacher@insa-rouen.fr.
Vincent
V
Levacher
D000110:Acetylcholinesterase / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D016503:Drug Delivery Systems; D005702:Galantamine / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism
C544515:1,4-dihydroquinoline; D002800:Cholinesterase Inhibitors; D011804:Quinolines; D005702:Galantamine; D000110:Acetylcholinesterase
Acetylcholinesterase (AChE) inhibitors; Blood brain barrier (BBB); Galantamine; Redox chemical delivery system