{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T14:23:35Z","timestamp":1787840615507,"version":"build-2784847793"},"reference-count":18,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Selective modulation of the serotonin 5-HT\u2082C receptor is a promising strategy for treating conditions, such as obesity and neuropsychiatric disorders. Aplysinopsins, a class of marine indole alkaloids, have emerged as potential 5-HT\u2082C-selective scaffolds.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>This work aims to assess the potential of aplysinopsin-based analogues as selective 5-HT\u2082C ligands.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Here, we present conducted an\n                      <jats:italic toggle=\"yes\">in silico<\/jats:italic>\n                      study of a library of aplysinopsin analogues and related indole alkaloids using induced-fit molecular docking, molecular dynamics (MD) simulations, and Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profiling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Dozens of analogues were docked into a serotonin receptor model, revealing sub-micromolar predicted binding affinities for several compounds. Top-ranked ligands, such as tubastrindole C, achieved docking scores around \u201312.7 kcal\/mol and maintained stable binding poses in 100-ns MD simulations. Key ligand\u2013receptor interactions included hydrogen bonding to the conserved Asp residue in the binding pocket and extensive \u03c0\u2013\u03c0 contacts with aromatic side chains. Notably, certain analogues with modest docking scores (e.g., N-propionyl-aplysinopsin) exhibited very favorable molecular mechanics generalized born surface area (MMGBSA) binding free energies, suggesting significant induced-fit effects upon binding. Predicted pharmacokinetic properties of the lead compounds were encouraging: all hits obeyed drug-likeness rules (0\u20131 Lipinski\u2019s rule violations) and showed high oral absorption prospects. While polar analogues had limited blood\u2013brain barrier permeability, several top candidates displayed moderate central nervous system (CNS) penetration scores.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>These results highlight aplysinopsin-based analogues as attractive selective 5-HT\u2082C ligand candidates and provide molecular insights to guide future optimization and experimental validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/jpbs.jpbs_1453_25","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T16:02:25Z","timestamp":1761753745000},"page":"166-173","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["From Sea to Synapse: Molecular Docking and Dynamics Study of Aplysinopsin Analogues as Selective 5-HT\u2082C Ligands"],"prefix":"10.4103","volume":"17","author":[{"given":"Abdelsattar M.","family":"Omar","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia"},{"name":"King Fahd Medical Research Center (KFMRC), King Abdulaziz University (KAU), Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hani Z.","family":"Asfour","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology and Immunology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hagar M.","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Analysis, College of Medical and Health Sciences, Liwa University, Abu Dhabi, United Arab of Emirates"},{"name":"Department of Applied Medical Chemistry, Medical Research Institute, Alexandria University, Alexandria, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabil A.","family":"Alhakamy","sequence":"additional","affiliation":[{"name":"Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah, Saudi Arabia"},{"name":"Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia"},{"name":"Mohamed Saeed Tamer Chair for Pharmaceutical Industries, King Abdulaziz University, Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gamal A.","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina S.","family":"El-Agamy","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrin R. 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