BIOMAT Database Logo BIOMAT Database Logo

Thiazole-substituted benzoylpiperazine derivatives as acetylcholinesterase inhibitors. 2018

Zafer Sahin, and Merve Ertas, and Ceysu Bender, and Emre F Bülbül, and Barkin Berk, and Sevde N Biltekin, and Leyla Yurttaş, and Şeref Demirayak
Department of Pharmaceutical Chemistry, Istanbul Medipol University, School of Pharmacy, Istanbul, Turkey.

Hit, Lead & Candidate Discovery After acetylcholine is released into the synaptic cleft, it is reabsorbed or deactivated by acetylcholinesterase (AChE). Studies on Alzheimer's disease (AD) in the mid-20th century proved that cognitive dysfunctions are associated with cholinergic neurotransmission. Drugs, such as tacrine, rivastigmine, donepezil, and galantamine are known as acetylcholinesterase inhibitors. However, these drugs have limited use in advanced AD and dementia. Recently, the anticholinesterase activity of various heterocyclic-framed compounds, including piperazine derivatives, has been investigated, and compounds with similar effects to known drugs have been identified. The aim of this study was to design new donepezil analogs. In this study, 66 original piperazinyl thiazole derivatives were synthesized by the reaction of piperazine N'-benzoyl thioamides and bromoacetophenones to inhibit AChE. Biological activity was measured by the Ellman method. Compounds 35, 38, 40, 45, 57, and 61 showed a high inhibitory effect among the series (80.36%-83.94% inhibition), and donepezil had a 96.42% inhibitory effect. The IC50 values of compounds 35, 38, and 40, were calculated as 0.9767 μM, 0.9493 μM, and 0.8023 μM, respectively. Compound 45 (IC50 = 1.122), Compound 57 (IC50 = 1.2130) and 61 (IC50 = 0.9193) also exhibited good activity on AChE. Molecular modeling studies were in agreement with the predictions. Trp286, Arg296, and Tyr341 were the key amino acids at the active site. Both donepezil and synthesized compounds seemed to interact with these residues.

UI MeSH Term Description Entries
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D002800 Cholinesterase Inhibitors Drugs that inhibit cholinesterases. The neurotransmitter ACETYLCHOLINE is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system. Acetylcholinesterase Inhibitor,Acetylcholinesterase Inhibitors,Anti-Cholinesterase,Anticholinesterase,Anticholinesterase Agent,Anticholinesterase Agents,Anticholinesterase Drug,Cholinesterase Inhibitor,Anti-Cholinesterases,Anticholinesterase Drugs,Anticholinesterases,Cholinesterase Inhibitors, Irreversible,Cholinesterase Inhibitors, Reversible,Agent, Anticholinesterase,Agents, Anticholinesterase,Anti Cholinesterase,Anti Cholinesterases,Drug, Anticholinesterase,Drugs, Anticholinesterase,Inhibitor, Acetylcholinesterase,Inhibitor, Cholinesterase,Inhibitors, Acetylcholinesterase,Inhibitors, Cholinesterase,Inhibitors, Irreversible Cholinesterase,Inhibitors, Reversible Cholinesterase,Irreversible Cholinesterase Inhibitors,Reversible Cholinesterase Inhibitors
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077265 Donepezil An indan and piperidine derivative that acts as a selective and reversible inhibitor of ACETYLCHOLINESTERASE. Donepezil is highly selective for the central nervous system and is used in the management of mild to moderate DEMENTIA in ALZHEIMER DISEASE. 1-Benzyl-4-((5,6-dimethoxy-1-indanon)-2-yl)methylpiperidine hydrochloride,Aricept,Donepezil Hydrochloride,Donepezilium Oxalate Trihydrate,E 2020,E-2020,E2020,Eranz
D000077489 Piperazine An anti-nematodal agent effective against the intestinal nematodes ASCARIS LUMBRICOIDES (roundworm) and ENTEROBIUS VERMICULARIS (pinworm, threadworm). It produces a neuromuscular block leading to flaccid muscle paralysis in susceptible worms, which are then dislodged from the gut and expelled in feces. 1,4-Diazacyclohexane,1,4-Piperazine,Piperazine Diacetate,Piperazine Dihydrochloride,Piperazine Hexahydrate,Piperazine Hydrate,Piperazine Hydrobromide,Piperazine Hydrochloride,Piperazine Monohydrochloride,Piperazine Phosphate,Piperazine Phosphate (1:1),Piperazine Phosphate Anhydrous,Piperazine Salt,Piperazine Sulfate,Piperazine Tartrate,Piperazine Tartrate (1:1), (R-(R*,R*))-isomer,Piperazine Tartrate, (R-(R*,R*))-isomer,Piperazinium Oleate,Pripsen,1,4 Diazacyclohexane,1,4 Piperazine
D000110 Acetylcholinesterase An enzyme that catalyzes the hydrolysis of ACETYLCHOLINE to CHOLINE and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC 3.1.1.7. Acetylcholine Hydrolase,Acetylthiocholinesterase,Hydrolase, Acetylcholine
D013844 Thiazoles Heterocyclic compounds where the ring system is composed of three CARBON atoms, a SULFUR and NITROGEN atoms. Thiazole
D062105 Molecular Docking Simulation A computer simulation technique that is used to model the interaction between two molecules. Typically the docking simulation measures the interactions of a small molecule or ligand with a part of a larger molecule such as a protein. Molecular Docking,Molecular Docking Simulations,Molecular Docking Analysis,Analysis, Molecular Docking,Docking Analysis, Molecular,Docking Simulation, Molecular,Docking, Molecular,Molecular Docking Analyses,Molecular Dockings,Simulation, Molecular Docking

Related Publications

Zafer Sahin, and Merve Ertas, and Ceysu Bender, and Emre F Bülbül, and Barkin Berk, and Sevde N Biltekin, and Leyla Yurttaş, and Şeref Demirayak
Synthesis of aminoalkyl-substituted aurone derivatives as acetylcholinesterase inhibitors.
January 2015, Bioorganic & medicinal chemistry,
Zafer Sahin, and Merve Ertas, and Ceysu Bender, and Emre F Bülbül, and Barkin Berk, and Sevde N Biltekin, and Leyla Yurttaş, and Şeref Demirayak
Synthesis of aminoalkyl-substituted coumarin derivatives as acetylcholinesterase inhibitors.
February 2014, Bioorganic & medicinal chemistry,
Zafer Sahin, and Merve Ertas, and Ceysu Bender, and Emre F Bülbül, and Barkin Berk, and Sevde N Biltekin, and Leyla Yurttaş, and Şeref Demirayak
Synthesis and Biological Evaluation of Thiazole-Based Derivatives as Potential Acetylcholinesterase Inhibitors.
July 2021, ACS omega,
Zafer Sahin, and Merve Ertas, and Ceysu Bender, and Emre F Bülbül, and Barkin Berk, and Sevde N Biltekin, and Leyla Yurttaş, and Şeref Demirayak
New 3-O-substituted xanthone derivatives as promising acetylcholinesterase inhibitors.
December 2021, Journal of enzyme inhibition and medicinal chemistry,
Zafer Sahin, and Merve Ertas, and Ceysu Bender, and Emre F Bülbül, and Barkin Berk, and Sevde N Biltekin, and Leyla Yurttaş, and Şeref Demirayak
Isoquinoline derivatives as potential acetylcholinesterase inhibitors.
April 2006, Bioorganic & medicinal chemistry letters,
Zafer Sahin, and Merve Ertas, and Ceysu Bender, and Emre F Bülbül, and Barkin Berk, and Sevde N Biltekin, and Leyla Yurttaş, and Şeref Demirayak
Chemiluminescent high-throughput microassay applied to imidazo[2,1-b]thiazole derivatives as potential acetylcholinesterase and butyrylcholinesterase inhibitors.
March 2008, European journal of medicinal chemistry,
Zafer Sahin, and Merve Ertas, and Ceysu Bender, and Emre F Bülbül, and Barkin Berk, and Sevde N Biltekin, and Leyla Yurttaş, and Şeref Demirayak
Design, synthesis and evaluation of new thiazole-piperazines as acetylcholinesterase inhibitors.
October 2013, Journal of enzyme inhibition and medicinal chemistry,
Zafer Sahin, and Merve Ertas, and Ceysu Bender, and Emre F Bülbül, and Barkin Berk, and Sevde N Biltekin, and Leyla Yurttaş, and Şeref Demirayak
Thiazole-substituted benzenesulfonamides as inhibitors of 12 human carbonic anhydrases.
April 2018, Bioorganic chemistry,
Zafer Sahin, and Merve Ertas, and Ceysu Bender, and Emre F Bülbül, and Barkin Berk, and Sevde N Biltekin, and Leyla Yurttaş, and Şeref Demirayak
p-Aminobenzoic acid derivatives as acetylcholinesterase inhibitors.
July 2005, European journal of medicinal chemistry,
Zafer Sahin, and Merve Ertas, and Ceysu Bender, and Emre F Bülbül, and Barkin Berk, and Sevde N Biltekin, and Leyla Yurttaş, and Şeref Demirayak
Novel pyridinium derivatives as inhibitors for acetylcholinesterase.
January 1996, Journal of enzyme inhibition,
Copied contents to your clipboard!