Abstract
In this manuscript we report an integrated study to develop simple choline esters as cholinergic agents potentially useful against the Alzheimer disease. In previously reported experiments we demonstrated the capability of the pivaloylcholine to exert cholinergic effects into the Central Nervous System, so we decided to explore small variants of choline esters. The knowledge of crystallographic models of the enzymes involved in the hydrolysis of the acetylcholine allowed to consider the steric compatibility of some choline derivatives within their catalytic sites. The purpose of the work was to find out analogues with increased selectivity toward the acetylcholinesterase versus the butyrrylcholinesterase. Theoretical models were compared to enzymatic tests carried out with both enzymes and two different methods. In this screening we have selected two candidates for the in vivo experiments with pre-treated rats. Their electroencephalographic profiles were recorded and averaged before and after the intraperitoneal treatment with two compounds in comparison to the pivaloyl lead ester. The results demonstrated that one of the esters can exert biological effects similar to the parent compound.
Keywords: Choline esters, Alzheimer's disease, molecular modelling, enzymatic inhibition, electrocortical activity
Current Pharmaceutical Design
Title: Simple Choline Esters as Potential Anti-Alzheimer Agents
Volume: 16 Issue: 6
Author(s): Stefano Alcaro, Rosaria Arcone, Giosue Costa, Daniela De Vita, Michelangelo Iannone, Francesco Ortuso, Antonio Procopio, Raffaele Pasceri, Domenicantonio Rotiroti and Luigi Scipione
Affiliation:
Keywords: Choline esters, Alzheimer's disease, molecular modelling, enzymatic inhibition, electrocortical activity
Abstract: In this manuscript we report an integrated study to develop simple choline esters as cholinergic agents potentially useful against the Alzheimer disease. In previously reported experiments we demonstrated the capability of the pivaloylcholine to exert cholinergic effects into the Central Nervous System, so we decided to explore small variants of choline esters. The knowledge of crystallographic models of the enzymes involved in the hydrolysis of the acetylcholine allowed to consider the steric compatibility of some choline derivatives within their catalytic sites. The purpose of the work was to find out analogues with increased selectivity toward the acetylcholinesterase versus the butyrrylcholinesterase. Theoretical models were compared to enzymatic tests carried out with both enzymes and two different methods. In this screening we have selected two candidates for the in vivo experiments with pre-treated rats. Their electroencephalographic profiles were recorded and averaged before and after the intraperitoneal treatment with two compounds in comparison to the pivaloyl lead ester. The results demonstrated that one of the esters can exert biological effects similar to the parent compound.
Export Options
About this article
Cite this article as:
Alcaro Stefano, Arcone Rosaria, Costa Giosue, De Vita Daniela, Iannone Michelangelo, Ortuso Francesco, Procopio Antonio, Pasceri Raffaele, Rotiroti Domenicantonio and Scipione Luigi, Simple Choline Esters as Potential Anti-Alzheimer Agents, Current Pharmaceutical Design 2010; 16 (6) . https://dx.doi.org/10.2174/138161210790883796
DOI https://dx.doi.org/10.2174/138161210790883796 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Serum Testosterone and Cognitive Function in Ageing Male: Updating the Evidence
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Recent Updates in the Alzheimer’s Disease Etiopathology and Possible Treatment Approaches: A Narrative Review of Current Clinical Trials
Current Molecular Pharmacology Nutraceuticals and "Repurposed" Drugs of Phytochemical Origin in Prevention and Interception of Chronic Degenerative Diseases and Cancer
Current Medicinal Chemistry Traumatic Brain Injury as a Risk Factor for Schizophrenia
Current Psychiatry Reviews Natural Anti-inflammatory Compounds as Drug Candidates in Alzheimer’s Disease
Current Medicinal Chemistry Transcriptomics Study of Neurodegenerative Disease: Emphasis on Synaptic Dysfunction Mechanism in Alzheimer's Disease
CNS & Neurological Disorders - Drug Targets Protein Aggregation and Self Assembly in Health and Disease
Current Proteomics The Role of VE-cadherin in Blood-brain Barrier Integrity Under Central Nervous System Pathological Conditions
Current Neuropharmacology The Clinical Impact of Quantitative Cell-free DNA, KRAS, and BRAF Mutations on Response to Anti-EGFR Treatment in Patients with Metastatic Colorectal Cancer
Current Pharmaceutical Design The Role of PGC-1α in the Pathogenesis of Neurodegenerative Disorders
Current Drug Targets Olfactory Dysfunction and Cognitive Impairment in Age-Related Neurodegeneration: Prevalence Related to Patient Selection, Diagnostic Criteria and Therapeutic Treatment of Aged Clients Receiving Clinical Neurology and Community-Based Care
Current Clinical Pharmacology 5-Hydroxymethylfurfural (HMF) in Organic Synthesis: A Review of its Recent Applications Towards Fine Chemicals
Current Organic Synthesis Memantine: A Therapeutic Approach in Treating Alzheimers and Vascular Dementia
Current Drug Targets - CNS & Neurological Disorders Genetic Bases of Progressive Supranuclear Palsy: The MAPT Tau Disease
Current Medicinal Chemistry Cholinergic Treatment of Traumatic Brain Injury
Current Drug Therapy Allocentric to Egocentric Spatial Switching: Impairment in aMCI and Alzheimer's Disease Patients?
Current Alzheimer Research Regression to the Mean: Implications for Clinical Trials of Psychotropic Agents in Dementia
Current Alzheimer Research GLP-1RA and SGLT2i: Cardiovascular Impact on Diabetic Patients
Current Hypertension Reviews The Effects of Combined Omega-3 Fatty Acids and Valproic Acid Supplementation on Symptoms of Borderline Personality Disorder: A Pilot Study
Current Psychopharmacology Proteomic Analysis of Alzheimers Disease Cerebrospinal Fluid from Neuropathologically Diagnosed Subjects
Current Alzheimer Research