Donepezil-Based Central Acetylcholinesterase Inhibitors by Means of a “Bio-Oxidizable” Prodrug Strategy: Design, Synthesis, and in Vitro Biological Evaluation

With the aim of reducing side effects of acetylcholinesterase inhibitors (AChEIs) during symptomatic treatment of Alzheimer’s disease, we report herein a new class of donepezil-based “bio-oxidizable” prodrugs 1 designed to be converted into dual binding site AChEIs 2. While most of indanone-derived...

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Published in:	Journal of medicinal chemistry Vol. 60; no. 13; pp. 5909 - 5926
Main Authors:	Peauger, Ludovic, Azzouz, Rabah, Gembus, Vincent, Ţînţaş, Mihaela-Liliana, Sopková-de Oliveira Santos, Jana, Bohn, Pierre, Papamicaël, Cyril, Levacher, Vincent
Format:	Journal Article
Language:	English
Published:	United States American Chemical Society 13-07-2017
Subjects:	Acetylcholinesterase - metabolism Alzheimer Disease - drug therapy Amyloid - antagonists & inhibitors Amyloid - metabolism Animals Chemical Sciences Cholinesterase Inhibitors - chemistry Cholinesterase Inhibitors - pharmacokinetics Cholinesterase Inhibitors - pharmacology Donepezil Drug Design Female Humans Indans - chemistry Indans - pharmacokinetics Indans - pharmacology Medicinal Chemistry Mice Molecular Docking Simulation Piperidines - chemistry Piperidines - pharmacokinetics Piperidines - pharmacology Prodrugs - chemistry Prodrugs - pharmacokinetics Prodrugs - pharmacology
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Abstract	With the aim of reducing side effects of acetylcholinesterase inhibitors (AChEIs) during symptomatic treatment of Alzheimer’s disease, we report herein a new class of donepezil-based “bio-oxidizable” prodrugs 1 designed to be converted into dual binding site AChEIs 2. While most of indanone-derived N-benzylpyridinium salts 2 revealed to be highly potent dual binding site hAChEIs (IC50 up to 3 nM), outperforming the standard drug donepezil (IC50 = 11 nM), most of the corresponding 1,4-dihydropyridines 1 were found to be inactive. Promisingly, whereas the selected prodrug 1r showed good permeability in the PAMPA-BBB model and high in vitro antioxidant activity, its conversion to AChEI 2r could be easily achieved under mild conditions when incubated in various oxidizing media. Lastly, both compounds 1r and 2r did not show genotoxicity in vitro and displayed high LD50 values in mice, making this prodrug 1r/drug 2r couple a good candidate for further in vivo biological experiments.
AbstractList	With the aim of reducing side effects of acetylcholinesterase inhibitors (AChEIs) during symptomatic treatment of Alzheimer's disease, we report herein a new class of donepezil-based "bio-oxidizable" prodrugs 1 designed to be converted into dual binding site AChEIs 2. While most of indanone-derived N-benzylpyridinium salts 2 revealed to be highly potent dual binding site hAChEIs (IC50 up to 3 nM), outperforming the standard drug donepezil (IC50 = 11 nM), most of the corresponding 1,4-dihydropyridines 1 were found to be inactive. Promisingly, whereas the selected prodrug 1r showed good permeability in the PAMPA-BBB model and high in vitro antioxidant activity, its conversion to AChEI 2r could be easily achieved under mild conditions when incubated in various oxidizing media. Lastly, both compounds 1r and 2r did not show genotoxicity in vitro and displayed high LD50 values in mice, making this prodrug 1r/drug 2r couple a good candidate for further in vivo biological experiments. With the aim of reducing side effects of acetylcholinesterase inhibitors (AChEIs) during symptomatic treatment of Alzheimer's disease, we report herein a new class of donepezil-based "bio-oxidizable" prodrugs 1 designed to be converted into dual binding site AChEIs 2. While most of indanone-derived N-benzylpyridinium salts 2 revealed to be highly potent dual binding site hAChEIs (IC up to 3 nM), outperforming the standard drug donepezil (IC = 11 nM), most of the corresponding 1,4-dihydropyridines 1 were found to be inactive. Promisingly, whereas the selected prodrug 1r showed good permeability in the PAMPA-BBB model and high in vitro antioxidant activity, its conversion to AChEI 2r could be easily achieved under mild conditions when incubated in various oxidizing media. Lastly, both compounds 1r and 2r did not show genotoxicity in vitro and displayed high LD values in mice, making this prodrug 1r/drug 2r couple a good candidate for further in vivo biological experiments.
Author	Papamicaël, Cyril Sopková-de Oliveira Santos, Jana Azzouz, Rabah Peauger, Ludovic Bohn, Pierre Gembus, Vincent Ţînţaş, Mihaela-Liliana Levacher, Vincent
AuthorAffiliation	VFP Therapies Univ Rouen, INSA Rouen, CNRS, IRCOF University of Rouen Université de Caen Department of Nuclear Medicine, Henri Becquerel Cancer Center and Rouen University Hospital and QuantIF LITIS (Equipe d’Accueil (EA) 4108-Federation Recherche (FR) National Center for Scientific Research (CNRS) 3638), Faculty of Medicine Centre d’Etudes et de Recherche sur le Médicament de Normandie Normandie Université, COBRA, UMR 6014 et FR 3038
AuthorAffiliation_xml	– name: University of Rouen – name: Centre d’Etudes et de Recherche sur le Médicament de Normandie – name: Department of Nuclear Medicine, Henri Becquerel Cancer Center and Rouen University Hospital and QuantIF LITIS (Equipe d’Accueil (EA) 4108-Federation Recherche (FR) National Center for Scientific Research (CNRS) 3638), Faculty of Medicine – name: Normandie Université, COBRA, UMR 6014 et FR 3038 – name: Univ Rouen, INSA Rouen, CNRS, IRCOF – name: Université de Caen – name: VFP Therapies
Author_xml	– sequence: 1 givenname: Ludovic surname: Peauger fullname: Peauger, Ludovic organization: VFP Therapies – sequence: 2 givenname: Rabah surname: Azzouz fullname: Azzouz, Rabah organization: VFP Therapies – sequence: 3 givenname: Vincent surname: Gembus fullname: Gembus, Vincent email: vgembus@vfp-therapies.com organization: VFP Therapies – sequence: 4 givenname: Mihaela-Liliana surname: Ţînţaş fullname: Ţînţaş, Mihaela-Liliana organization: Univ Rouen, INSA Rouen, CNRS, IRCOF – sequence: 5 givenname: Jana surname: Sopková-de Oliveira Santos fullname: Sopková-de Oliveira Santos, Jana organization: Université de Caen – sequence: 6 givenname: Pierre surname: Bohn fullname: Bohn, Pierre organization: University of Rouen – sequence: 7 givenname: Cyril surname: Papamicaël fullname: Papamicaël, Cyril organization: Univ Rouen, INSA Rouen, CNRS, IRCOF – sequence: 8 givenname: Vincent orcidid: 0000-0002-6429-1965 surname: Levacher fullname: Levacher, Vincent email: vincent.levacher@insa-rouen.fr organization: Univ Rouen, INSA Rouen, CNRS, IRCOF
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Cites_doi	10.1016/j.neuroscience.2015.04.039 10.1016/j.jalz.2014.02.001 10.1016/j.bmc.2010.07.012 10.2174/1381612043383313 10.1021/jm8001313 10.1016/j.ejmech.2014.01.017 10.1039/b903041g 10.1016/j.bmcl.2015.09.063 10.1007/s10562-011-0660-9 10.1126/science.1166305 10.1016/S0006-2952(02)01514-9 10.1016/S0969-2126(99)80040-9 10.1021/jm7009364 10.1021/acs.jmedchem.5b01119 10.1016/S1359-6446(02)02332-2 10.1097/NEN.0b013e3181cb5af4 10.2174/092986706776360978 10.1021/jm300871x 10.1159/000113688 10.1586/14737175.5.1.101 10.1016/0006-2952(61)90145-9 10.1111/j.1471-4159.1993.tb13610.x 10.1007/BF01234480 10.1038/srep33172 10.1016/S0896-6273(00)80108-7 10.1016/j.ejmech.2015.02.009 10.1021/jm701491k 10.2174/138161206778792985 10.1002/anie.200700256 10.1517/14740338.3.5.425 10.1038/aps.2016.87 10.1039/C6MD00053C 10.1002/9781118407738 10.1021/jm970715l 10.1021/jm020531t 10.1016/j.bmcl.2012.04.029 10.1111/j.1749-6632.1987.tb45809.x 10.1016/S0040-4020(01)00076-X 10.1002/pro.5560020312 10.2174/1381612043383412 10.1371/journal.pone.0144337 10.1002/jhet.2031 10.1016/j.pneurobio.2015.12.003 10.1007/s12640-009-9121-2 10.1016/j.ejmech.2013.07.038 10.1016/S0023-6438(95)80008-5 10.1016/S0169-409X(98)00090-8 10.1038/1811199a0 10.1021/ol302593z 10.1155/2016/1892412 10.1016/S1383-5718(97)00172-1 10.1126/science.6857264 10.2174/0929867003375191 10.1038/nrn1035 10.1016/S0076-6879(99)09020-5 10.1155/S1110724302203010 10.1021/bi0101392 10.1056/NEJMra0909142 10.1021/acs.jmedchem.6b00426 10.1155/2013/316523 10.1021/jm401047q 10.1021/bi00680a029 10.1016/S1383-5718(00)00019-X 10.1017/S1041610203008676 10.1016/j.bmc.2015.03.051 10.1016/j.ejmech.2015.08.061 10.1016/0165-1161(83)90010-9 10.1021/cn5003539 10.1073/pnas.0508575102 10.1016/S0960-894X(02)00482-1 10.1016/j.bmc.2012.08.052 10.1016/S0163-7258(97)00098-3
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References	ref9/cit9 ref45/cit45 ref3/cit3 ref27/cit27 ref63/cit63 ref56/cit56 ref16/cit16 ref52/cit52 ref23/cit23 ref8/cit8 ref31/cit31 ref59/cit59 ref2/cit2 ref34/cit34 ref71/cit71 ref37/cit37 ref20/cit20 ref48/cit48 ref60/cit60 ref17/cit17 ref10/cit10 ref35/cit35 ref53/cit53 ref19/cit19 ref21/cit21 ref42/cit42 ref46/cit46 ref49/cit49 ref13/cit13 ref61/cit61 ref67/cit67 ref24/cit24 ref38/cit38 ref50/cit50 ref64/cit64 ref54/cit54 ref6/cit6 ref36/cit36 ref18/cit18 ref65/cit65 ref25/cit25 ref29/cit29 ref72/cit72 ref32/cit32 ref39/cit39 ref14/cit14 ref57/cit57 ref5/cit5 ref51/cit51 ref43/cit43 Bodor N. (ref33/cit33) 2012 ref28/cit28 ref40/cit40 ref68/cit68 ref26/cit26 ref55/cit55 ref73/cit73 ref69/cit69 ref12/cit12 ref15/cit15 ref62/cit62 ref66/cit66 ref41/cit41 ref58/cit58 ref22/cit22 ref4/cit4 ref30/cit30 ref47/cit47 ref1/cit1 Alvarez A. (ref11/cit11) 1998; 18 ref44/cit44 ref70/cit70 ref7/cit7
References_xml	– ident: ref52/cit52 doi: 10.1016/j.neuroscience.2015.04.039 – ident: ref1/cit1 doi: 10.1016/j.jalz.2014.02.001 – ident: ref40/cit40 doi: 10.1016/j.bmc.2010.07.012 – ident: ref14/cit14 doi: 10.2174/1381612043383313 – ident: ref17/cit17 doi: 10.1021/jm8001313 – ident: ref43/cit43 doi: 10.1016/j.ejmech.2014.01.017 – ident: ref38/cit38 doi: 10.1039/b903041g – ident: ref46/cit46 doi: 10.1016/j.bmcl.2015.09.063 – ident: ref66/cit66 doi: 10.1007/s10562-011-0660-9 – ident: ref34/cit34 doi: 10.1126/science.1166305 – ident: ref67/cit67 doi: 10.1016/S0006-2952(02)01514-9 – ident: ref27/cit27 doi: 10.1016/S0969-2126(99)80040-9 – ident: ref16/cit16 doi: 10.1021/jm7009364 – ident: ref20/cit20 doi: 10.1021/acs.jmedchem.5b01119 – ident: ref32/cit32 doi: 10.1016/S1359-6446(02)02332-2 – ident: ref5/cit5 doi: 10.1097/NEN.0b013e3181cb5af4 – ident: ref4/cit4 doi: 10.2174/092986706776360978 – ident: ref28/cit28 doi: 10.1021/jm300871x – ident: ref23/cit23 doi: 10.1159/000113688 – ident: ref50/cit50 doi: 10.1586/14737175.5.1.101 – ident: ref53/cit53 doi: 10.1016/0006-2952(61)90145-9 – ident: ref63/cit63 doi: 10.1111/j.1471-4159.1993.tb13610.x – ident: ref73/cit73 doi: 10.1007/BF01234480 – ident: ref25/cit25 doi: 10.1038/srep33172 – ident: ref10/cit10 doi: 10.1016/S0896-6273(00)80108-7 – ident: ref44/cit44 doi: 10.1016/j.ejmech.2015.02.009 – ident: ref55/cit55 doi: 10.1021/jm701491k – ident: ref15/cit15 doi: 10.2174/138161206778792985 – ident: ref22/cit22 doi: 10.1002/anie.200700256 – ident: ref7/cit7 doi: 10.1517/14740338.3.5.425 – ident: ref26/cit26 doi: 10.1038/aps.2016.87 – ident: ref62/cit62 doi: 10.1039/C6MD00053C – volume: 18 start-page: 3213 year: 1998 ident: ref11/cit11 publication-title: J. Mol. Biol. contributor: fullname: Alvarez A. – volume-title: Retrometabolic Drug Design and Targeting year: 2012 ident: ref33/cit33 doi: 10.1002/9781118407738 contributor: fullname: Bodor N. – ident: ref36/cit36 doi: 10.1021/jm970715l – ident: ref37/cit37 doi: 10.1021/jm020531t – ident: ref64/cit64 doi: 10.1016/j.bmcl.2012.04.029 – ident: ref29/cit29 doi: 10.1111/j.1749-6632.1987.tb45809.x – ident: ref47/cit47 doi: 10.1016/S0040-4020(01)00076-X – ident: ref57/cit57 doi: 10.1002/pro.5560020312 – ident: ref13/cit13 doi: 10.2174/1381612043383412 – ident: ref8/cit8 doi: 10.1371/journal.pone.0144337 – ident: ref61/cit61 doi: 10.1002/jhet.2031 – ident: ref19/cit19 doi: 10.1016/j.pneurobio.2015.12.003 – ident: ref24/cit24 doi: 10.1007/s12640-009-9121-2 – ident: ref42/cit42 doi: 10.1016/j.ejmech.2013.07.038 – ident: ref60/cit60 doi: 10.1016/S0023-6438(95)80008-5 – ident: ref31/cit31 doi: 10.1016/S0169-409X(98)00090-8 – ident: ref69/cit69 doi: 10.1038/1811199a0 – ident: ref65/cit65 doi: 10.1021/ol302593z – ident: ref59/cit59 doi: 10.1155/2016/1892412 – ident: ref71/cit71 doi: 10.1016/S1383-5718(97)00172-1 – ident: ref35/cit35 doi: 10.1126/science.6857264 – ident: ref54/cit54 doi: 10.2174/0929867003375191 – ident: ref49/cit49 doi: 10.1038/nrn1035 – ident: ref68/cit68 doi: 10.1016/S0076-6879(99)09020-5 – ident: ref3/cit3 doi: 10.1155/S1110724302203010 – ident: ref12/cit12 doi: 10.1021/bi0101392 – ident: ref2/cit2 doi: 10.1056/NEJMra0909142 – ident: ref21/cit21 doi: 10.1021/acs.jmedchem.6b00426 – ident: ref6/cit6 doi: 10.1155/2013/316523 – ident: ref18/cit18 doi: 10.1021/jm401047q – ident: ref56/cit56 doi: 10.1021/bi00680a029 – ident: ref72/cit72 doi: 10.1016/S1383-5718(00)00019-X – ident: ref48/cit48 doi: 10.1017/S1041610203008676 – ident: ref58/cit58 doi: 10.1016/j.bmc.2015.03.051 – ident: ref45/cit45 doi: 10.1016/j.ejmech.2015.08.061 – ident: ref70/cit70 doi: 10.1016/0165-1161(83)90010-9 – ident: ref9/cit9 doi: 10.1021/cn5003539 – ident: ref51/cit51 doi: 10.1073/pnas.0508575102 – ident: ref39/cit39 doi: 10.1016/S0960-894X(02)00482-1 – ident: ref41/cit41 doi: 10.1016/j.bmc.2012.08.052 – ident: ref30/cit30 doi: 10.1016/S0163-7258(97)00098-3
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Snippet	With the aim of reducing side effects of acetylcholinesterase inhibitors (AChEIs) during symptomatic treatment of Alzheimer’s disease, we report herein a new... With the aim of reducing side effects of acetylcholinesterase inhibitors (AChEIs) during symptomatic treatment of Alzheimer's disease, we report herein a new...
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SubjectTerms	Acetylcholinesterase - metabolism Alzheimer Disease - drug therapy Amyloid - antagonists & inhibitors Amyloid - metabolism Animals Chemical Sciences Cholinesterase Inhibitors - chemistry Cholinesterase Inhibitors - pharmacokinetics Cholinesterase Inhibitors - pharmacology Donepezil Drug Design Female Humans Indans - chemistry Indans - pharmacokinetics Indans - pharmacology Medicinal Chemistry Mice Molecular Docking Simulation Piperidines - chemistry Piperidines - pharmacokinetics Piperidines - pharmacology Prodrugs - chemistry Prodrugs - pharmacokinetics Prodrugs - pharmacology
Title	Donepezil-Based Central Acetylcholinesterase Inhibitors by Means of a “Bio-Oxidizable” Prodrug Strategy: Design, Synthesis, and in Vitro Biological Evaluation
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