Abstract
Background: Benzimidazole is an interesting pharmacophore which has been extensively studied in medicinal chemistry due to its high affinity towards various enzymes and receptors. Its derivatives have been previously shown to possess a wide range of biological activities including anthelmintic, antihypertensive, antiulcer, as well as anticholinesterase activity.
Objective: The objective of this study is to search for more potent benzimidazole-based cholinesterase inhibitors, through the modification of the 1- and 2-positions of the benzimidazole core.
Methods: Synthesis of compounds were carried out via a 4-step reaction scheme following a previously reported protocol. Structure-activity relationship of the compounds are established through in vitro cholinesterase assays and in silico docking studies. Furthermore, cytotoxicity and blood brain barrier (BBB) permeability of the compounds were also investigated.
Results: Among the synthesised compounds, three of them (5IIa, 5IIb, and 5IIc) exhibited potent selective butyrylcholinesterase inhibition at low micromolar level. The compounds did not show any significant cytotoxicity when tested against a panel of human cell lines. Moreover, the most active compound, 5IIc, was highly permeable across the blood brain barrier.
Conclusion: In total 10 benzimidazole derivatives were synthesized and screened for their AChE and BuChE inhibitory activities. Lead compound 5Iic, represents a valuable compound for further development as potential AD therapeutics.
Keywords: Benzimidazoles, cholinesterase, Alzheimer’s disease, butyrylcholinesterase, blood-brain barrier, selective inhibitors.
Current Alzheimer Research
Title:Synthesis, Molecular Docking, and Biological Evaluation of Benzimidazole Derivatives as Selective Butyrylcholinesterase Inhibitors
Volume: 17 Issue: 13
Author(s): Zhe Y. Ha, Hoay C. Ong, Chuan W. Oo and Keng Y. Yeong*
Affiliation:
- School of Science, Monash University Malaysia Campus, Jalan Lagoon Selatan, Bandar Sunway, 47500, Selangor,Malaysia
Keywords: Benzimidazoles, cholinesterase, Alzheimer’s disease, butyrylcholinesterase, blood-brain barrier, selective inhibitors.
Abstract:
Background: Benzimidazole is an interesting pharmacophore which has been extensively studied in medicinal chemistry due to its high affinity towards various enzymes and receptors. Its derivatives have been previously shown to possess a wide range of biological activities including anthelmintic, antihypertensive, antiulcer, as well as anticholinesterase activity.
Objective: The objective of this study is to search for more potent benzimidazole-based cholinesterase inhibitors, through the modification of the 1- and 2-positions of the benzimidazole core.
Methods: Synthesis of compounds were carried out via a 4-step reaction scheme following a previously reported protocol. Structure-activity relationship of the compounds are established through in vitro cholinesterase assays and in silico docking studies. Furthermore, cytotoxicity and blood brain barrier (BBB) permeability of the compounds were also investigated.
Results: Among the synthesised compounds, three of them (5IIa, 5IIb, and 5IIc) exhibited potent selective butyrylcholinesterase inhibition at low micromolar level. The compounds did not show any significant cytotoxicity when tested against a panel of human cell lines. Moreover, the most active compound, 5IIc, was highly permeable across the blood brain barrier.
Conclusion: In total 10 benzimidazole derivatives were synthesized and screened for their AChE and BuChE inhibitory activities. Lead compound 5Iic, represents a valuable compound for further development as potential AD therapeutics.
Export Options
About this article
Cite this article as:
Ha Y. Zhe , Ong C. Hoay , Oo W. Chuan and Yeong Y. Keng *, Synthesis, Molecular Docking, and Biological Evaluation of Benzimidazole Derivatives as Selective Butyrylcholinesterase Inhibitors, Current Alzheimer Research 2020; 17 (13) . https://dx.doi.org/10.2174/1567205018666210218151228
DOI https://dx.doi.org/10.2174/1567205018666210218151228 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...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
-
High-Throughput Screening Technologies for Botulinum Neurotoxins
Current Topics in Medicinal Chemistry Interventional Radiology in Paediatrics
Current Pediatric Reviews Dendritoma Vaccine for Cancer: A Hopeful Approach
Current Cancer Therapy Reviews Enzymatic Properties and Physiological Roles of Cytosolic 5’-Nucleotidase II.
Current Medicinal Chemistry Voltage-Gated Sodium Channels in Neurological Disorders
CNS & Neurological Disorders - Drug Targets The Role of Autophagy in the Pathogenesis of Ischemic Stroke
Current Neuropharmacology KRAS: A Promising Therapeutic Target for Cancer Treatment
Current Topics in Medicinal Chemistry Immune System Modulates the Function of Adult Neural Stem Cells
Current Immunology Reviews (Discontinued) Resisting the Sun with Vitamin D
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Small Molecule Tyrosine Kinase Inhibitors: Potential Role in Pediatric Malignant Solid Tumors
Current Cancer Drug Targets Current Management of Neonatal Liver Tumors
Current Pediatric Reviews Iron Chelating Strategies in Systemic Metal Overload, Neurodegeneration and Cancer
Current Medicinal Chemistry The Association Between Alcohol Use and the Progression of Alzheimer’s Disease
Current Alzheimer Research Histone Deacetylase Inhibitors: From Chromatin Remodeling to Experimental Cancer Therapeutics
Current Medicinal Chemistry The Relationship Between Oncogene Expression and Clinical Outcome in Endometrial Carcinoma
Current Cancer Drug Targets Molecular Mechanisms of Neuronal Histamine and its Receptors in Obesity
Current Molecular Pharmacology Different Aspects of Head and Neck Squamous Cell Carcinoma: Cancer Stem Cells, their Niche and Targeted Therapy
Current Stem Cell Research & Therapy Current Status and Future Perspective for Research on Medicinal Plants with Anticancerous Activity and Minimum Cytotoxic Value
Current Drug Targets Chemical Properties and Mechanisms Determining the Anti-Cancer Action of Garlic-Derived Organic Sulfur Compounds
Anti-Cancer Agents in Medicinal Chemistry Bacterial Toxins: Potential Weapons Against HIV Infection
Current Pharmaceutical Design