Synthesis, Biological Evaluation and Molecular Docking Study of Hydrazone-Containing Pyridinium Salts as Cholinesterase Inhibitors

Autor: Ercin Erciyas, Sülünay Parlar, Gulsah Bayraktar, Ayse Hande Tarikogullari, Vildan Alptüzün
Přispěvatelé: Ege Üniversitesi
Rok vydání: 2016
Předmět:
Pyridinium Compounds
Stereochemistry
Hydrazone
01 natural sciences
chemistry.chemical_compound
Structure-Activity Relationship
Bromide
Drug Discovery
Structure–activity relationship
Humans
Benzofuran
Butyrylcholinesterase
chemistry.chemical_classification
Pyridinium salt
Dose-Response Relationship
Drug
Molecular Structure
010405 organic chemistry
Butyrylcholinesterase inhibitor
ComputerSystemsOrganization_COMPUTER-COMMUNICATIONNETWORKS
Hydrazones
General Chemistry
General Medicine
Acetylcholinesterase
0104 chemical sciences
Molecular Docking Simulation
010404 medicinal & biomolecular chemistry
ComputingMilieux_MANAGEMENTOFCOMPUTINGANDINFORMATIONSYSTEMS
ComputingMethodologies_PATTERNRECOGNITION
chemistry
Acetylcholinesterase inhibitor
Salts
Pyridinium
Cholinesterase Inhibitors
InformationSystems_MISCELLANEOUS
Docking study
Zdroj: Chemicalpharmaceutical bulletin. 64(9)
ISSN: 1347-5223
2758-1632
Popis: WOS: 000382352700006
PubMed ID: 27581632
A series of pyridinium salts bearing alkylphenyl groups at 1 position and hydrazone structure at 4 position of the pyridinium ring were synthesized and evaluated for the inhibition of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. The cholinesterase (ChE) inhibitory activity studies were carried out by using the Ellman's colorimetric method. All compounds displayed considerable AChE and BuChE inhibitory activity and some of the compounds manifested remarkable anti-AChE activity compared to the reference compound, galantamine. Among the title compounds, the series including benzofuran aromatic ring exhibited the best inhibitory activity both on AChE and BuChE enzymes. Compound 3b, 4-[2-(1-(benzofuran-2-yl)ethylidene)hydrazinyl]-1-(3-Phenylpropyl)pyridinium bromide, was the most active compound with IC50 value of 0.23 (0.24) mu m against enantiomeric excess (ee)AChE (human (h)AChE) while compound 3a, 4-[2-(1-(benzofuran-2-yl)ethylidene)hydrazinyl]-1-phenethylpyridinium bromide, was the most active compound with IC50 value of 0.95 mu m against BuChE. Moreover, 3a and b exhibited higher activity than the reference compound galantamine (eeAChE (hAChE) IC50 0.43 (0.52) mu m; BuChE IC50 14.92 mu m). Molecular docking studies were carried out on 3b having highest inhibitory activity against AChE.
Research Grants from Ege University [13/Ecz/026]
This study was supported by Research Grants from Ege University (Project Number: 13/Ecz/026). The authors would like to thank the Pharmaceutical Sciences Research Centre (FABAL) at Ege University Faculty of Pharmacy for spectral analyses of the compounds.
Databáze: OpenAIRE
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