title: Synthesis, Biological Evaluation and Molecular Docking Study of Hydrazone-Containing Pyridinium Salts as Cholinesterase Inhibitors.
abstract: 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) µM 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 µM against BuChE. Moreover, 3a and b exhibited higher activity than the reference compound galantamine (eeAChE (hAChE) IC50 0.43 (0.52) µM; BuChE IC50 14.92 µM). Molecular docking studies were carried out on 3b having highest inhibitory activity against AChE.
authors: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ege University.
authors: Sulunay
authors: S
authors: Parlar
authors: Gulsah
authors: G
authors: Bayraktar
authors: Ayse Hande
authors: AH
authors: Tarikogullari
authors: Vildan
authors: V
authors: Alptüzün
authors: Ercin
authors: E
authors: Erciyas
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011726:Pyridinium Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012492:Salts / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D002800:Cholinesterase Inhibitors; D006835:Hydrazones; D011726:Pyridinium Compounds; D012492:Salts; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase