Pharmacophore-based virtual screening for identification of marine sponge bioactive compound inhibitors against Alzheimer's disease
Alzheimer's disease is a hereditary neurodegenerative disease that occurs sporadically and causes amnestic cognitive impairment. Traditional drug discovery methods have faced challenges in this regard, leading researchers to explore natural products as potential therapeutics. Marine sponges are...
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Elsevier
2025-06-01
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| Series: | Chemical Physics Impact |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667022424003499 |
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| author | Suruthi SS Prashanth KK Baskaran A |
| author_facet | Suruthi SS Prashanth KK Baskaran A |
| author_sort | Suruthi SS |
| collection | DOAJ |
| description | Alzheimer's disease is a hereditary neurodegenerative disease that occurs sporadically and causes amnestic cognitive impairment. Traditional drug discovery methods have faced challenges in this regard, leading researchers to explore natural products as potential therapeutics. Marine sponges are rich in diverse range of bioactive compounds with promising biological activities. In this study, AChE, SLC6A4, 5-HT1A, TrkB, and GABA are chosen as the target proteins, which focuses on ache, serotonin, GABA, and neurotropic pathways. A bioactive compound library from marine sponges was prepared by retrieving a list from the CMNP database. The compounds were screened using a chronological index and Drug likeness rules where 2,504 compounds were filtered out based on their molecular weight and the selected compounds undergone secondary screening using pharmacology filters to assess their absorption, distribution, metabolism, and excretion (ADME) properties. Virtual screening was performed using PyRx with selected target proteins. Four compounds namely Xestosaprol D, Xestosaprol E, Xestosaprol J, and 14, 15-dihydroxymethyl Xestoquinone were found to interact with all the chosen protein. Among 4 compounds, Xestosaprol J showed better binding energy of -7.7, -9.9, -8.4, -9.2, and -8.1 kcal/mol. Further, the best interacting AchE-Xestosaprol J complex along with standard AchE Agonist Donepezil was subjected to Molecular dynamics simulation and analysis, which maintained its stability between 65 and 85 ns with RMSD value ranging between 0- 3.5 Å in the virtual biological environment. Overall, Xestosaprol J showed better physicochemical and ADME properties, suggesting their potential as drug candidates, but further investigations are needed to determine their specific biological activities in-vitro. |
| format | Article |
| id | doaj-art-933ee47922274a64b2e755980e1758c4 |
| institution | Kabale University |
| issn | 2667-0224 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Chemical Physics Impact |
| spelling | doaj-art-933ee47922274a64b2e755980e1758c42025-01-12T05:26:12ZengElsevierChemical Physics Impact2667-02242025-06-0110100805Pharmacophore-based virtual screening for identification of marine sponge bioactive compound inhibitors against Alzheimer's diseaseSuruthi SS0Prashanth KK1Baskaran A2Research Scholar, School of Life Sciences, B.S. Abdur Rahman Crescent Institute of Science and Technology, IndiaSimbioen Labs and Scientific Services Private Limited, Vandalur, Chennai 600 048, IndiaResearch Scholar, School of Life Sciences, B.S. Abdur Rahman Crescent Institute of Science and Technology, India; Corresponding author at Assistant Professor, School of Life Sciences, B.S. Abdur Rahman Crescent Institute of Science and Technology, Vandalur, Tamil Nadu 600 048.Alzheimer's disease is a hereditary neurodegenerative disease that occurs sporadically and causes amnestic cognitive impairment. Traditional drug discovery methods have faced challenges in this regard, leading researchers to explore natural products as potential therapeutics. Marine sponges are rich in diverse range of bioactive compounds with promising biological activities. In this study, AChE, SLC6A4, 5-HT1A, TrkB, and GABA are chosen as the target proteins, which focuses on ache, serotonin, GABA, and neurotropic pathways. A bioactive compound library from marine sponges was prepared by retrieving a list from the CMNP database. The compounds were screened using a chronological index and Drug likeness rules where 2,504 compounds were filtered out based on their molecular weight and the selected compounds undergone secondary screening using pharmacology filters to assess their absorption, distribution, metabolism, and excretion (ADME) properties. Virtual screening was performed using PyRx with selected target proteins. Four compounds namely Xestosaprol D, Xestosaprol E, Xestosaprol J, and 14, 15-dihydroxymethyl Xestoquinone were found to interact with all the chosen protein. Among 4 compounds, Xestosaprol J showed better binding energy of -7.7, -9.9, -8.4, -9.2, and -8.1 kcal/mol. Further, the best interacting AchE-Xestosaprol J complex along with standard AchE Agonist Donepezil was subjected to Molecular dynamics simulation and analysis, which maintained its stability between 65 and 85 ns with RMSD value ranging between 0- 3.5 Å in the virtual biological environment. Overall, Xestosaprol J showed better physicochemical and ADME properties, suggesting their potential as drug candidates, but further investigations are needed to determine their specific biological activities in-vitro.http://www.sciencedirect.com/science/article/pii/S2667022424003499Pharmacology filtersDockingMolecular dynamicsDrug likenessCognitive impairmentSponges |
| spellingShingle | Suruthi SS Prashanth KK Baskaran A Pharmacophore-based virtual screening for identification of marine sponge bioactive compound inhibitors against Alzheimer's disease Chemical Physics Impact Pharmacology filters Docking Molecular dynamics Drug likeness Cognitive impairment Sponges |
| title | Pharmacophore-based virtual screening for identification of marine sponge bioactive compound inhibitors against Alzheimer's disease |
| title_full | Pharmacophore-based virtual screening for identification of marine sponge bioactive compound inhibitors against Alzheimer's disease |
| title_fullStr | Pharmacophore-based virtual screening for identification of marine sponge bioactive compound inhibitors against Alzheimer's disease |
| title_full_unstemmed | Pharmacophore-based virtual screening for identification of marine sponge bioactive compound inhibitors against Alzheimer's disease |
| title_short | Pharmacophore-based virtual screening for identification of marine sponge bioactive compound inhibitors against Alzheimer's disease |
| title_sort | pharmacophore based virtual screening for identification of marine sponge bioactive compound inhibitors against alzheimer s disease |
| topic | Pharmacology filters Docking Molecular dynamics Drug likeness Cognitive impairment Sponges |
| url | http://www.sciencedirect.com/science/article/pii/S2667022424003499 |
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