{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T15:18:36Z","timestamp":1782227916601,"version":"3.54.5"},"reference-count":50,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education (MOE) and the Busan Metropolitan City","award":["2025-RISE-02-003"],"award-info":[{"award-number":["2025-RISE-02-003"]}]},{"name":"Ministry of Education, Science, and Technology, Republic of Korea","award":["RS-2023-00253188"],"award-info":[{"award-number":["RS-2023-00253188"]}]},{"name":"Ministry of Education, Republic of Korea","award":["RS-2025-25440216"],"award-info":[{"award-number":["RS-2025-25440216"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Cholinergic dysfunction is a hallmark of Alzheimer\u2019s disease (AD), driven by elevated acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity that depletes acetylcholine and contributes to amyloid pathology. Current AD treatments face major challenges, including poor brain penetration, short effect duration and safety concerns, highlighting the need for compounds suitable for preventive or earlier-stage intervention. This study investigated marine phytohormones as modulators of cholinergic imbalance, using an integrative strategy encompassing enzymatic assays, QSAR and DFT calculations, molecular docking, molecular dynamics (MD) simulations, and ADMET profiling. Among them, isopentenyl adenine (IPA) and abscisic acid (ABA) showed inhibitory activity against cholinesterases. IPA inhibited both AChE and BChE through distinct mechanisms with noncompetitive inhibition of AChE and competitive inhibition of BChE, while ABA showed selective noncompetitive inhibition of AChE. DFT-based analysis revealed distinct electronic properties supporting differential reactivity. Moreover, IPA interacted with both catalytic and peripheral residues in AChE, and aligned with BChE\u2019s active site, while ABA was bound more peripherally. MD simulations confirmed complex-specific conformational stability based on RMSD, RMSF, Rg, and hydrogen bonding analysis. Both compounds showed low off-target potential against serine proteases and favorable predicted ADMET profiles. These results support the potential of marine phytohormones as preventive modulators of cholinergic dysfunction in AD.<\/jats:p>","DOI":"10.3390\/md24010035","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T12:52:17Z","timestamp":1767963137000},"page":"35","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Structural and Mechanistic Insights into Dual Cholinesterase Inhibition by Marine Phytohormones"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3124-2665","authenticated-orcid":false,"given":"Kumju","family":"Youn","sequence":"first","affiliation":[{"name":"Department of Food Science and Nutrition, Dong-A University, Busan 49315, Republic of Korea"},{"name":"Center for Food & Bio Innovation, Dong-A University, Busan 49315, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4195-9230","authenticated-orcid":false,"given":"Legie Mae","family":"Soriano","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, The Graduate School of Dong-A University, Busan 49315, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira","family":"Jun","sequence":"additional","affiliation":[{"name":"Department of Food Science and Nutrition, Dong-A University, Busan 49315, Republic of Korea"},{"name":"Center for Food & Bio Innovation, Dong-A University, Busan 49315, Republic of Korea"},{"name":"Department of Health Sciences, The Graduate School of Dong-A University, Busan 49315, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,9]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025, October 16). 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