Hecogenin a Plant Derived Small Molecule as an Antagonist to BACE-1: A Potential Target for Neurodegenerative Disorders
The field of drug discovery has recognized the significance of computer-aided drug design. Recent advancements in structure identification and characterization, bio-computational science and molecular biology have significantly contributed to the development of novel treatments for various diseases....
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MDPI AG
2023-06-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/13/6/758 |
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| author | Deepthi Padmanabhan Manzer H. Siddiqui Purushothaman Natarajan Senthilkumar Palanisamy |
| author_facet | Deepthi Padmanabhan Manzer H. Siddiqui Purushothaman Natarajan Senthilkumar Palanisamy |
| author_sort | Deepthi Padmanabhan |
| collection | DOAJ |
| description | The field of drug discovery has recognized the significance of computer-aided drug design. Recent advancements in structure identification and characterization, bio-computational science and molecular biology have significantly contributed to the development of novel treatments for various diseases. Alzheimer’s disease is prevalent in over 50 million affected people, with the pathological condition of amyloidal plaque formation by the beta-amyloidal peptide that results in lesions of the patient’s brain, thus making the target prediction and treatment a hurdle. In this study, we evaluated the potential of 54 bioactive compounds from <i>Justicia adhatoda L.</i> and <i>Sida cordifolia L.</i> identified through LC-MS/MS against the β-site amyloid precursor cleaving enzyme (beta-secretase) that results in the formation of amyloidal plaques. To study the drug-likeness of the phytocompounds, Lipinski’s rule of five for ADME profiling and toxicity prediction was performed. Molecular docking was performed using auto-dock tool of PyRx software; molecular dynamic simulations were performed using the Schrodinger suite. Molecular docking against BACE-1 protein revealed that hecogenin, identified from <i>S. cordifolia</i> has a broad spectrum of pharmacological applications and a binding affinity score of −11.3 kcal/Mol. The Hecogenin–BACE-1 protein complex was found to be stable after 30 ns of MD simulation, resulting in its substantial stability. Further studies focusing on the in vivo neuroprotective activity of hecogenin against the disease will pave the way for efficient drug discovery from natural sources in a precise manner. |
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| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-11T02:10:38Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-a64a774f42e64cf597d55c7f9131b7d62023-11-18T11:35:16ZengMDPI AGMetabolites2218-19892023-06-0113675810.3390/metabo13060758Hecogenin a Plant Derived Small Molecule as an Antagonist to BACE-1: A Potential Target for Neurodegenerative DisordersDeepthi Padmanabhan0Manzer H. Siddiqui1Purushothaman Natarajan2Senthilkumar Palanisamy3Department of Genetic Engineering, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603203, IndiaDepartment of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Biology, West Virginia State University, Institute, WV 25112-1000, USADepartment of Genetic Engineering, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603203, IndiaThe field of drug discovery has recognized the significance of computer-aided drug design. Recent advancements in structure identification and characterization, bio-computational science and molecular biology have significantly contributed to the development of novel treatments for various diseases. Alzheimer’s disease is prevalent in over 50 million affected people, with the pathological condition of amyloidal plaque formation by the beta-amyloidal peptide that results in lesions of the patient’s brain, thus making the target prediction and treatment a hurdle. In this study, we evaluated the potential of 54 bioactive compounds from <i>Justicia adhatoda L.</i> and <i>Sida cordifolia L.</i> identified through LC-MS/MS against the β-site amyloid precursor cleaving enzyme (beta-secretase) that results in the formation of amyloidal plaques. To study the drug-likeness of the phytocompounds, Lipinski’s rule of five for ADME profiling and toxicity prediction was performed. Molecular docking was performed using auto-dock tool of PyRx software; molecular dynamic simulations were performed using the Schrodinger suite. Molecular docking against BACE-1 protein revealed that hecogenin, identified from <i>S. cordifolia</i> has a broad spectrum of pharmacological applications and a binding affinity score of −11.3 kcal/Mol. The Hecogenin–BACE-1 protein complex was found to be stable after 30 ns of MD simulation, resulting in its substantial stability. Further studies focusing on the in vivo neuroprotective activity of hecogenin against the disease will pave the way for efficient drug discovery from natural sources in a precise manner.https://www.mdpi.com/2218-1989/13/6/758phytocompoundsneurodegenerative diseasesplant therapeuticsmedicinal plantsdrug discovery |
| spellingShingle | Deepthi Padmanabhan Manzer H. Siddiqui Purushothaman Natarajan Senthilkumar Palanisamy Hecogenin a Plant Derived Small Molecule as an Antagonist to BACE-1: A Potential Target for Neurodegenerative Disorders Metabolites phytocompounds neurodegenerative diseases plant therapeutics medicinal plants drug discovery |
| title | Hecogenin a Plant Derived Small Molecule as an Antagonist to BACE-1: A Potential Target for Neurodegenerative Disorders |
| title_full | Hecogenin a Plant Derived Small Molecule as an Antagonist to BACE-1: A Potential Target for Neurodegenerative Disorders |
| title_fullStr | Hecogenin a Plant Derived Small Molecule as an Antagonist to BACE-1: A Potential Target for Neurodegenerative Disorders |
| title_full_unstemmed | Hecogenin a Plant Derived Small Molecule as an Antagonist to BACE-1: A Potential Target for Neurodegenerative Disorders |
| title_short | Hecogenin a Plant Derived Small Molecule as an Antagonist to BACE-1: A Potential Target for Neurodegenerative Disorders |
| title_sort | hecogenin a plant derived small molecule as an antagonist to bace 1 a potential target for neurodegenerative disorders |
| topic | phytocompounds neurodegenerative diseases plant therapeutics medicinal plants drug discovery |
| url | https://www.mdpi.com/2218-1989/13/6/758 |
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