New Coumarin Derivatives as Cholinergic and Cannabinoid System Modulators.
Alzheimer Disease
/ drug therapy
Amidohydrolases
Amyloid beta-Peptides
/ metabolism
Animals
Blood-Brain Barrier
/ drug effects
Cannabinoids
/ chemistry
Carbamates
/ pharmacology
Chemistry, Pharmaceutical
/ methods
Cholinergic Agents
Coumarins
/ therapeutic use
Drug Design
Endocannabinoids
/ metabolism
Enzyme Inhibitors
/ pharmacology
Humans
Inhibitory Concentration 50
Molecular Docking Simulation
Protein Conformation
Rats
Receptors, Cannabinoid
Receptors, Cholinergic
/ chemistry
Rivastigmine
/ pharmacology
AChE
Alzheimer’s disease
Aβ42 self-aggregation
BuChE
CB receptors
FAAH
amide
carbamate
Journal
Molecules (Basel, Switzerland)
ISSN: 1420-3049
Titre abrégé: Molecules
Pays: Switzerland
ID NLM: 100964009
Informations de publication
Date de publication:
28 May 2021
28 May 2021
Historique:
received:
26
04
2021
revised:
21
05
2021
accepted:
26
05
2021
entrez:
2
6
2021
pubmed:
3
6
2021
medline:
23
7
2021
Statut:
epublish
Résumé
In the last years, the connection between the endocannabinoid system (eCS) and neuroprotection has been discovered, and evidence indicates that eCS signaling is involved in the regulation of cognitive processes and in the pathophysiology of Alzheimer's disease (AD). Accordingly, pharmacotherapy targeting eCS could represent a valuable contribution in fighting a multifaceted disease such as AD, opening a new perspective for the development of active agents with multitarget potential. In this paper, a series of coumarin-based carbamic and amide derivatives were designed and synthesized as multipotent compounds acting on cholinergic system and eCS-related targets. Indeed, they were tested with appropriate enzymatic assays on acetyl and butyryl-cholinesterases and on fatty acid amide hydrolase (FAAH), and also evaluated as cannabinoid receptor (CB1 and CB2) ligands. Moreover, their ability to reduce the self-aggregation of beta amyloid protein (Aβ
Identifiants
pubmed: 34071439
pii: molecules26113254
doi: 10.3390/molecules26113254
pmc: PMC8198714
pii:
doi:
Substances chimiques
Amyloid beta-Peptides
0
Cannabinoids
0
Carbamates
0
Cholinergic Agents
0
Coumarins
0
Endocannabinoids
0
Enzyme Inhibitors
0
Receptors, Cannabinoid
0
Receptors, Cholinergic
0
Amidohydrolases
EC 3.5.-
fatty-acid amide hydrolase
EC 3.5.1.-
Rivastigmine
PKI06M3IW0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Références
J Enzyme Inhib Med Chem. 2020 Dec;35(1):1462-1470
pubmed: 32779543
J Med Chem. 2014 Sep 25;57(18):7590-9
pubmed: 25148591
ACS Med Chem Lett. 2012 Jan 21;3(3):182-6
pubmed: 24900454
J Med Chem. 2012 Nov 26;55(22):10282-6
pubmed: 23035744
Transl Neurodegener. 2018 Jan 30;7:2
pubmed: 29423193
Biochem Pharmacol. 1961 Jul;7:88-95
pubmed: 13726518
Neurobiol Aging. 2012 Aug;33(8):1522-32
pubmed: 21546126
J Med Chem. 2014 Oct 9;57(19):8167-79
pubmed: 25226236
Pharmacol Res. 2007 Nov;56(5):382-92
pubmed: 17950616
J Med Chem. 2016 Jul 14;59(13):6387-406
pubmed: 27309570
Prostaglandins Other Lipid Mediat. 2013 Apr-May;102-103:13-30
pubmed: 23474290
J Med Chem. 2008 Feb 14;51(3):347-72
pubmed: 18181565
Chembiochem. 2007 Nov 23;8(17):2152-61
pubmed: 17939148
Behav Brain Res. 2011 Aug 10;221(2):334-40
pubmed: 20060018
Curr Pharm Des. 2009;15(6):587-600
pubmed: 19199984
J Med Chem. 2020 Jul 9;63(13):7369-7391
pubmed: 32515588
J Med Chem. 2004 Nov 18;47(24):5945-52
pubmed: 15537349
J Med Chem. 2017 Jan 12;60(1):4-46
pubmed: 27766867
J Med Chem. 2004 Oct 7;47(21):4998-5008
pubmed: 15456244
J Mol Biol. 2010 Jul 23;400(4):743-54
pubmed: 20493882
Curr Neuropharmacol. 2019;17(2):176-183
pubmed: 29962346
Lab Invest. 1991 Jul;65(1):104-10
pubmed: 1906561
ACS Chem Neurosci. 2019 Feb 20;10(2):852-862
pubmed: 30521323
Arch Biochem Biophys. 2013 Aug 1;536(1):1-5
pubmed: 23689009
J Med Chem. 2020 Nov 12;63(21):12290-12358
pubmed: 32686940
Brain. 2018 Jul 1;141(7):1917-1933
pubmed: 29850777
Curr Neuropharmacol. 2010 Mar;8(1):69-80
pubmed: 20808547
Science. 2002 Nov 29;298(5599):1793-6
pubmed: 12459591
Expert Opin Drug Discov. 2009 Jul;4(7):763-784
pubmed: 20544003
J Prev Alzheimers Dis. 2019;6(1):2-15
pubmed: 30569080
Future Med Chem. 2019 May;11(9):1057-1082
pubmed: 31140865
Nat Rev Drug Discov. 2008 May;7(5):438-55
pubmed: 18446159
J Neurosci. 2003 Dec 3;23(35):11136-41
pubmed: 14657172
J Med Chem. 2016 Jan 14;59(1):114-31
pubmed: 26632651
Rev Physiol Biochem Pharmacol. 2008;160:1-24
pubmed: 18481028
Pharmacol Rev. 2010 Dec;62(4):588-631
pubmed: 21079038
Science. 1966 Oct 21;154(3747):400-2
pubmed: 5917090
Molecules. 2020 Jul 13;25(14):
pubmed: 32668631
Proc Natl Acad Sci U S A. 2005 Nov 22;102(47):17213-8
pubmed: 16275899