Abstract
Background: Alzheimer disease (AD) can be considered as the most common age related neurodegenerative disorder and also an important cause of death in elderly patients. A number of studies showed the correlation of this disease pathology with BACE1 inhibitor and it is also evident that BACE1 inhibitor can function as a very potent strategy in treating AD.
Methods: In this present study, we aimed to prospect for novel plant-derived BACE1 inhibitors from Leea indica and to realise structural basis of their interactions and mechanisms using combined molecular docking and molecular dynamics based approaches. An extensive library of Leea indica plant derived molecule was compiled and computationally screened for inhibitory action against BACE1 by using virtual screening approaches. Furthermore, induced fit docking and classical molecular dynamics along with steered molecular dynamics simulations were employed to get insight of the binding mechanisms.
Results: Two triterpenoids, ursolic acid and lupeol were identified through virtual screening; wherein, lupeol showed better binding free energy in MM/GBSA, MM/PBSA and MM/GBVI approaches. Furthermore classical and steered dynamics revealed the favourable hydrophobic interactions between the lupeol and the residues of flap or catalytic dyadof BACE1; however, ursolic acid showed disfavorable interactions with the BACE1.
Conclusion: This study therefore unveiled the potent BACE1 inhibitor from a manually curated dataset of Leea indica molecules, which may provide a novel dimension of designing novel BACE1 inhibitors for AD therapy.
Keywords: BACE1, steered molecular dynamics, triterpenoids, Leea. indica, virtual screening, ursolic acid, Alzheimer disease.
Current Pharmaceutical Design
Title:Prospecting and Structural Insight into the Binding of Novel Plant-Derived Molecules of Leea indica as Inhibitors of BACE1
Volume: 24 Issue: 33
Author(s): S.M. Zahid Hosen*, Maruf Rubayed, Raju Dash, Md. Junaid, Sarmistha Mitra, Muhammad Shaiful Alam and Rupantar Dey
Affiliation:
- Molecular Modeling and Drug Design Laboratory, Pharmacology Research Division, Bangladesh Council of Scientific and Industrial Research, Chittagong-4220,Bangladesh
Keywords: BACE1, steered molecular dynamics, triterpenoids, Leea. indica, virtual screening, ursolic acid, Alzheimer disease.
Abstract: Background: Alzheimer disease (AD) can be considered as the most common age related neurodegenerative disorder and also an important cause of death in elderly patients. A number of studies showed the correlation of this disease pathology with BACE1 inhibitor and it is also evident that BACE1 inhibitor can function as a very potent strategy in treating AD.
Methods: In this present study, we aimed to prospect for novel plant-derived BACE1 inhibitors from Leea indica and to realise structural basis of their interactions and mechanisms using combined molecular docking and molecular dynamics based approaches. An extensive library of Leea indica plant derived molecule was compiled and computationally screened for inhibitory action against BACE1 by using virtual screening approaches. Furthermore, induced fit docking and classical molecular dynamics along with steered molecular dynamics simulations were employed to get insight of the binding mechanisms.
Results: Two triterpenoids, ursolic acid and lupeol were identified through virtual screening; wherein, lupeol showed better binding free energy in MM/GBSA, MM/PBSA and MM/GBVI approaches. Furthermore classical and steered dynamics revealed the favourable hydrophobic interactions between the lupeol and the residues of flap or catalytic dyadof BACE1; however, ursolic acid showed disfavorable interactions with the BACE1.
Conclusion: This study therefore unveiled the potent BACE1 inhibitor from a manually curated dataset of Leea indica molecules, which may provide a novel dimension of designing novel BACE1 inhibitors for AD therapy.
Export Options
About this article
Cite this article as:
Hosen Zahid S.M.*, Rubayed Maruf , Dash Raju , Junaid Md. , Mitra Sarmistha , Alam Shaiful Muhammad and Dey Rupantar , Prospecting and Structural Insight into the Binding of Novel Plant-Derived Molecules of Leea indica as Inhibitors of BACE1, Current Pharmaceutical Design 2018; 24 (33) . https://dx.doi.org/10.2174/1381612824666181106111020
DOI https://dx.doi.org/10.2174/1381612824666181106111020 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
Blood-based biomarkers in large-scale screening for neurodegenerative diseases
Disease biomarkers are necessary tools that can be employ in several clinical context of use (COU), ranging from the (early) diagnosis, prognosis, prediction, to monitor of disease state and/or drug efficacy. Regarding neurodegenerative diseases, in particular Alzheimer’s disease (AD), a battery of well-validated biomarkers are available, such as cerebrospinal fluid ...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
Diabetes mellitus: advances in diagnosis and treatment driving by precision medicine
Diabetes mellitus (DM) is a chronic degenerative metabolic disease with ever increasing prevalence worldwide which is now an epidemic disease affecting 500 million people worldwide. Insufficient insulin secretion from pancreatic β cells unable to maintain blood glucose homeostasis is the main feature of this disease. Multifactorial and complex nature of ...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
- 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
-
Neurotoxins: Free Radical Mechanisms and Melatonin Protection
Current Neuropharmacology The Impact of Traditional Chinese Medicine on Mitophagy in Disease Models
Current Pharmaceutical Design Histone Deacetylase Inhibitors Modulating Non-epigenetic Players: The Novel Mechanism for Small Molecule Based Therapeutic Intervention
Current Drug Targets Chronic Diseases and COVID-19: A Review
Endocrine, Metabolic & Immune Disorders - Drug Targets Disorders of Innate Immunity in Human ageing and effects of Nutraceutical Administration
Endocrine, Metabolic & Immune Disorders - Drug Targets Psychomotor Seizure Test, Neurotoxicity and in vitro Neuroprotection Assay of some Semicarbazone Analogues
Central Nervous System Agents in Medicinal Chemistry Lipid Alterations in the Earliest Clinically Recognizable Stage of Alzheimers Disease: Implication of the Role of Lipids in the Pathogenesis of Alzheimers Disease
Current Alzheimer Research Crossing the Blood-Brain Barrier: A Review on Drug Delivery Strategies for Treatment of the Central Nervous System Diseases
Current Drug Delivery Transgenic Mouse Models of Tauopathy in Drug Discovery
CNS & Neurological Disorders - Drug Targets The Characteristics of Entorhinal Cortex Functional Connectivity in Alzheimer’s Disease Patients with Depression
Current Alzheimer Research Gonadotropin-Releasing Hormone Receptor System: Modulatory Role in Aging and Neurodegeneration
CNS & Neurological Disorders - Drug Targets Mitochondrial Fusion and Fission Proteins Expression Dynamically Change in a Murine Model of Amyotrophic Lateral Sclerosis
Current Neurovascular Research Creatine and the Liver: Metabolism and Possible Interactions
Mini-Reviews in Medicinal Chemistry Conformations and Biological Activities of Amyloid Beta Peptide 25-35
Current Protein & Peptide Science Aging and Neuroinflammatory Disorders: New Biomarkers and Therapeutic Targets
Current Pharmaceutical Design Type 2 Diabetes Mellitus: New Genetic Insights will Lead to New Therapeutics
Current Genomics The Anti-Inflammatory Role of Minocycline in Alzheimer´s Disease
Current Alzheimer Research HSP27: Mechanisms of Cellular Protection Against Neuronal Injury
Current Molecular Medicine Pathogenic Role of Serine Protease HtrA2/Omi in Neurodegenerative Diseases
Current Protein & Peptide Science Cholesterol and Alzheimers Disease: Clinical and Experimental Models Suggest Interactions of Different Genetic, Dietary and Environmental Risk Factors
Current Drug Targets