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Synthesis, in vitro screening and molecular docking of isoquinolinium-5-carbaldoximes as acetylcholinesterase and butyrylcholinesterase reactivators
- Source :
- Journal of Enzyme Inhibition and Medicinal Chemistry, Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 35, Iss 1, Pp 478-488 (2020)
- Publication Year :
- 2020
- Publisher :
- Taylor & Francis, 2020.
-
Abstract
- The series of symmetrical and unsymmetrical isoquinolinium-5-carbaldoximes was designed and prepared for cholinesterase reactivation purposes. The novel compounds were evaluated for intrinsic acetylcholinesterase (AChE) or butyrylcholinesterase (BChE) inhibition, when the majority of novel compounds resulted with high inhibition of both enzymes and only weak inhibitors were selected for reactivation experiments on human AChE or BChE inhibited by sarin, VX, or paraoxon. The AChE reactivation for all used organophosphates was found negligible if compared to the reactivation ability of obidoxime. Importantly, two compounds were found to reactivate BChE inhibited by sarin or VX better to obidoxime at human attainable concentration. One compound resulted as better reactivator of NEMP (VX surrogate)-inhibited BChE than obidoxime. The in vitro results were further rationalized by molecular docking studies showing future directions on designing potent BChE reactivators.<br />GRAPHICAL ABSTRACT
- Subjects :
- Cholinesterase Reactivators
Stereochemistry
organophosphate
RM1-950
01 natural sciences
oxime
chemistry.chemical_compound
Drug Discovery
Humans
Butyrylcholinesterase
Cholinesterase
Pharmacology
biology
010405 organic chemistry
Organophosphate
General Medicine
Oxime
Isoquinolines
Acetylcholinesterase
In vitro
0104 chemical sciences
reactivator
Molecular Docking Simulation
010404 medicinal & biomolecular chemistry
chemistry
biology.protein
Therapeutics. Pharmacology
Cholinesterase Inhibitors
Research Paper
Subjects
Details
- Language :
- English
- ISSN :
- 14756374 and 14756366
- Volume :
- 35
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of Enzyme Inhibition and Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....3e5c2dccaa60abd51ca9c69bd7bb9046