{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T09:08:39Z","timestamp":1774948119258,"version":"3.50.1"},"reference-count":63,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Tay Nguyen University\n              https:\/\/ror.org\/01s7bde64","award":["T2025-46CBT\u0110"],"award-info":[{"award-number":["T2025-46CBT\u0110"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) remains a significant global health challenge, highlighting the need for novel dual inhibitors targeting acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). This study investigated the trunk bark of Terminalia triptera Stapf. as a potential source of bioactive secondary metabolites for AD management. Bioassay-guided isolation led to the identification of two flavan-3-ol derivatives, epicatechin-(4\u03b2\u21928)-ent-catechin (1) and (\u2212)-catechin (2), reported here for the first time from this species. In vitro assays demonstrated that the dimeric compound 1 exhibited stronger dual inhibitory activity against AChE and BChE, with IC50 values of 4.41 \u00d7 10\u22124 and 4.75 \u00d7 10\u22124 mol\/L, respectively, surpassing the reference compound berberine chloride. Molecular docking analysis revealed that compound 1 formed extensive interactions within both catalytic and peripheral anionic sites of the enzymes. Density Functional Theory (DFT) calculations indicated high kinetic stability, reflected by large HOMO\u2013LUMO energy gaps (6.66\u20136.97 eV), while global reactivity descriptors suggested lower electrophilicity (\u03c9 = 2.19\u20132.34 eV), supporting a potentially favorable safety profile. Furthermore, 100 ns molecular dynamics simulations confirmed stable ligand\u2013protein complexes stabilized by hydrogen-bond networks and deep binding within catalytic pockets. Overall, these findings highlight T. triptera and its dimeric proanthocyanidins as promising multi-target candidates for anti-Alzheimer drug development.<\/jats:p>","DOI":"10.3390\/molecules31071113","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T14:33:33Z","timestamp":1774622013000},"page":"1113","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Isolation, Identification and In Silico Evaluation of Novel Cholinesterase Inhibitors from Terminalia triptera Stapf."],"prefix":"10.3390","volume":"31","author":[{"given":"Tu Quy","family":"Phan","sequence":"first","affiliation":[{"name":"Department of Science and Technology, Tay Nguyen University, Dak Lak 630000, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3154-4353","authenticated-orcid":false,"given":"Hung Tse","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Chinese Materia Medica Development, National Research Institute of Chinese Medicine, Taipei 11221, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1384-3731","authenticated-orcid":false,"given":"San-Lang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Tamkang University, New Taipei City 25137, Taiwan"},{"name":"Life Science Development Center, Tamkang University, New Taipei City 25137, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dinh Sy","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Science and Technology, Tay Nguyen University, Dak Lak 630000, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1229-7839","authenticated-orcid":false,"given":"Manh Dung","family":"Doan","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology and Environment, Tay Nguyen University, Dak Lak 630000, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thi Huyen Thoa","family":"Pham","sequence":"additional","affiliation":[{"name":"Department of Science and Technology, Tay Nguyen University, Dak Lak 630000, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thi Kim Thu","family":"Phan","sequence":"additional","affiliation":[{"name":"Department of Science and Technology, Tay Nguyen University, Dak Lak 630000, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ba Phong","family":"Truong","sequence":"additional","affiliation":[{"name":"Department of Science and Technology, Tay Nguyen University, Dak Lak 630000, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2666-9584","authenticated-orcid":false,"given":"Van Bon","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology and Environment, Tay Nguyen University, Dak Lak 630000, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2026, February 10). Dementia: Key Facts. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/dementia."},{"key":"ref_2","unstructured":"Alzheimer\u2019s Disease International (2022). World Alzheimer Report 2022: Life After Diagnosis: Navigating Treatment, Care and Support, Alzheimer\u2019s Disease International. Available online: https:\/\/www.alzint.org\/resource\/world-alzheimer-report-2022\/."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2865","DOI":"10.1002\/alz.12901","article-title":"The worldwide costs of dementia in 2019","volume":"19","author":"Wimo","year":"2023","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"217","DOI":"10.31887\/DCNS.2009.11.2\/hbrodaty","article-title":"Family caregivers of people with dementia","volume":"11","author":"Brodaty","year":"2009","journal-title":"Dialogues Clin. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.cell.2019.09.001","article-title":"Alzheimer disease: An update on pathobiology and treatment strategies","volume":"179","author":"Long","year":"2019","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s13024-019-0333-5","article-title":"The neuropathological diagnosis of Alzheimer\u2019s disease","volume":"14","author":"DeTure","year":"2019","journal-title":"Mol. Neurodegener."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1093\/brain\/awy132","article-title":"The cholinergic system in the pathophysiology and treatment of Alzheimer\u2019s disease","volume":"141","author":"Hampel","year":"2018","journal-title":"Brain"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"101","DOI":"10.2174\/1570159X13666150716165726","article-title":"Alzheimer\u2019s disease: Targeting the cholinergic system","volume":"14","author":"Guimaraes","year":"2016","journal-title":"Curr. Neuropharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"315","DOI":"10.2174\/1570159X11311030006","article-title":"Acetylcholinesterase inhibitors: Pharmacology and toxicology","volume":"11","year":"2013","journal-title":"Curr. Neuropharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/s12272-013-0036-3","article-title":"A review on cholinesterase inhibitors for Alzheimer\u2019s disease","volume":"36","author":"Anand","year":"2013","journal-title":"Arch. Pharmacal Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/ptr.1280","article-title":"Plants with traditional uses and activities, relevant to the management of Alzheimer\u2019s disease and other cognitive disorders","volume":"17","author":"Howes","year":"2003","journal-title":"Phytother. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"379","DOI":"10.2174\/1570159X11311040003","article-title":"Nature: A substantial source of auspicious substances with acetylcholinesterase inhibitory action","volume":"11","author":"Orhan","year":"2013","journal-title":"Curr. Neuropharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"ALNasser, M.N., Alboraiy, G.M., Alsowig, E.M., and Alqattan, F.M. (2025). Cholinesterase inhibitors from plants and their potential in Alzheimer\u2019s treatment: Systematic review. Brain Sci., 15.","DOI":"10.3390\/brainsci15020215"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/s13659-019-00222-3","article-title":"The genus Terminalia (Combretaceae): An ethnopharmacological, phytochemical and pharmacological review","volume":"9","author":"Zhang","year":"2019","journal-title":"Nat. Prod. Bioprospect."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s10787-015-0246-z","article-title":"The medicinal properties and phytochemistry of plants of the genus Terminalia (Combretaceae)","volume":"23","author":"Cock","year":"2015","journal-title":"Inflammopharmacology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1124\/pr.112.007336","article-title":"Computational Methods in Drug Discovery","volume":"66","author":"Sliwoski","year":"2014","journal-title":"Pharmacol. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.2174\/1568026614666140929124445","article-title":"Structure-Based Virtual Screening for Drug Discovery: Principles, Applications and Recent Advances","volume":"14","author":"Lionta","year":"2014","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1016\/j.neuron.2018.08.011","article-title":"Molecular Dynamics Simulation for All","volume":"99","author":"Hollingsworth","year":"2018","journal-title":"Neuron"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"42717","DOI":"10.1038\/srep42717","article-title":"SwissADME: A Free Web Tool to Evaluate Pharmacokinetics, Drug-Likeness and Medicinal Chemistry Friendliness of Small Molecules","volume":"7","author":"Daina","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3351","DOI":"10.1007\/s11164-025-05591-8","article-title":"Inside into diverse pharmaceutical properties and phytochemical profiles of Tetrastigma erubescens: A drug discovery via experiments, docking, DFT, ADMET and Lipinski\u2019s rules of five performance","volume":"51","author":"Phan","year":"2025","journal-title":"Res. Chem. Intermed."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Phan, T.K.P., Wang, S.-L., Nguyen, Q.V., Phan, T.Q., Nguyen, T.T., Tran, T.T.T., Nguyen, A.D., Nguyen, V.B., and Doan, M.D. (2023). Assessment of the Chemical Profile and Potential Medical Effects of a Flavonoid-Rich Extract of Eclipta prostrata L. Collected in the Central Highlands of Vietnam. Pharmaceuticals, 16.","DOI":"10.3390\/ph16101476"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5567","DOI":"10.1007\/s11164-023-05126-z","article-title":"Phytochemical profiles and novel biofunctions of Dillenia ovata Wall. ex Hook.f. et Thomson: A Vietnamese indigenous medicinal plant","volume":"49","author":"Doan","year":"2023","journal-title":"Res. Chem. Intermed."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Thang, P.N.T., Tran, V.-H., Vu, T.A., Vinh, N.N., Huynh, D.T.M., and Pham, D.T. (2022). Determination of Antioxidant, Cytotoxicity, and Acetylcholinesterase Inhibitory Activities of Alkaloids Isolated from Sophora flavescens Ait. Grown in Dak Nong, Vietnam. Pharmaceuticals, 15.","DOI":"10.3390\/ph15111384"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.sajb.2021.11.016","article-title":"In vitro antioxidant, anticholinesterase inhibitory, and antimicrobial activity studies of Terminalia chebula (Retz) and Terminalia arjuna (Roxb)","volume":"146","author":"Khan","year":"2022","journal-title":"S. Afr. J. Bot."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"123115","DOI":"10.1016\/j.saa.2023.123115","article-title":"Inhibition mechanisms of four ellagitannins from Terminalia chebula fruits on acetylcholinesterase by inhibition kinetics, spectroscopy and molecular docking analyses","volume":"302","author":"Li","year":"2023","journal-title":"Spectrochim. Acta Part A Mol. Biomol. Spectrosc."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"de Torre, M.P., Cavero, R.Y., and Calvo, M.I. (2022). Anticholinesterase Activity of Selected Medicinal Plants from Navarra Region of Spain and a Detailed Phytochemical Investigation of Origanum vulgare L. ssp. vulgare. Molecules, 27.","DOI":"10.3390\/molecules27207100"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2387","DOI":"10.1021\/acs.jnatprod.8b00953","article-title":"Proanthocyanidin Dimers and Trimers from Vitis vinifera Provide Diverse Structural Motifs for the Evaluation of Dentin Biomodification","volume":"82","author":"Phansalkar","year":"2019","journal-title":"J. Nat. Prod."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1080\/14786419.2017.1309536","article-title":"Antioxidant phenolic compounds from the rhizomes of Astilbe rivularis","volume":"32","author":"Hori","year":"2018","journal-title":"Nat. Prod. Res."},{"key":"ref_29","first-page":"111","article-title":"A study on phytochemical and pharmacological activity of Terminalia arjuna: A review","volume":"15","author":"Swain","year":"2023","journal-title":"Res. J. Pharmacogn. Phytochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1016\/j.phytochem.2010.03.018","article-title":"Polyphenolic compounds in the fruits of Egyptian medicinal plants (Terminalia bellerica, Terminalia chebula and Terminalia horrida): Characterization, quantitation and determination of antioxidant capacities","volume":"71","author":"Pfundstein","year":"2010","journal-title":"Phytochemistry"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.jep.2013.02.025","article-title":"Metabolite Profiling of Polyphenols in Terminalia spp","volume":"147","author":"Pellati","year":"2013","journal-title":"J. Ethnopharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Okello, E.J., and Mather, J. (2020). Comparative Kinetics of Acetyl- and Butyryl-Cholinesterase Inhibition by Green Tea Catechins|Relevance to the Symptomatic Treatment of Alzheimer\u2019s Disease. Nutrients, 12.","DOI":"10.3390\/nu12041090"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Cichon, N., Grabowska, W., Gorniak, L., Stela, M., Harmata, P., Ceremuga, M., and Bijak, M. (2025). Mechanistic and Therapeutic Insights into Flavonoid-Based Inhibition of Acetylcholinesterase: Implications for Neurodegenerative Diseases. Nutrients, 17.","DOI":"10.3390\/nu17010078"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4265","DOI":"10.1021\/jm030266r","article-title":"A specific mechanism of nonspecific inhibition","volume":"46","author":"McGovern","year":"2003","journal-title":"J. Med. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"18277","DOI":"10.1039\/C6RA27872H","article-title":"Molecular Docking, Molecular Dynamics Simulation, Biological Evaluation and 2D QSAR Analysis of Flavonoids from Syzygium Alternifolium as Potent Anti-Helicobacter Pylori Agents","volume":"7","author":"Rajesh","year":"2017","journal-title":"RSC Adv."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1126\/science.1678899","article-title":"Atomic structure of acetylcholinesterase from Torpedo californica: A prototypic acetylcholine-binding protein","volume":"253","author":"Sussman","year":"1991","journal-title":"Science"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"41141","DOI":"10.1074\/jbc.M210241200","article-title":"Crystal structure of human butyrylcholinesterase and of its complexes with substrate and products","volume":"278","author":"Nicolet","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1038\/nrd1851","article-title":"Predicting in vivo drug interactions from in vitro drug discovery data","volume":"4","author":"Wienkers","year":"2005","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s12951-018-0392-8","article-title":"Nano based drug delivery systems: Recent developments and future prospects","volume":"16","author":"Patra","year":"2018","journal-title":"J. Nanobiotechnol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/S0031-8914(34)90011-2","article-title":"\u00dcber die Zuordnung von Wellenfunktionen und Eigenwerten zu den einzelnen Elektronen eines Atoms","volume":"1","author":"Koopmans","year":"1934","journal-title":"Physica"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"7512","DOI":"10.1021\/ja00364a005","article-title":"Absolute hardness: Companion parameter to absolute electronegativity","volume":"105","author":"Parr","year":"1983","journal-title":"J. Am. Chem. Soc."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1021\/ja983494x","article-title":"Electrophilicity index","volume":"121","author":"Parr","year":"1999","journal-title":"J. Am. Chem. Soc."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2705","DOI":"10.1021\/ja0276063","article-title":"HSAB Principle Applied to the Time Evolution of Chemical Reactions","volume":"125","author":"Chattaraj","year":"2003","journal-title":"J. Am. Chem. Soc."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e202500994","DOI":"10.1002\/cbdv.202500994","article-title":"New Record of Potential Tyrosinase Inhibitory, Antioxidant, and Photoprotective Effects of Vietnamese Castanea mollissima Extracts","volume":"22","author":"Vu","year":"2025","journal-title":"Chem. Biodivers."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1073\/pnas.44.2.98","article-title":"Application of a Theory of Enzyme Specificity to Protein Synthesis","volume":"44","author":"Koshland","year":"1958","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.bpj.2009.11.011","article-title":"Determination of Ensemble-Average Pairwise Root Mean Square Deviation from Experimental Serial Crystallography Data","volume":"98","author":"Kuzmanic","year":"2010","journal-title":"Biophys. J."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Salo-Ahen, O.M.H., Alanko, I., Bhadane, R., Bonvin, A.M.J.J., Honorato, R.V., Hossain, S., Juffer, A.H., Kabedev, A., Lahtela-Kakkonen, M., and Larsen, A.S. (2021). Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development. Processes, 9.","DOI":"10.3390\/pr9010071"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1134\/S0026893308040195","article-title":"Radius of Gyration as an Indicator of Protein Structure Compactness","volume":"42","author":"Lobanov","year":"2008","journal-title":"Mol. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Patil, R., Das, S., Stanley, A., Yadav, L., Sudhakar, A., and Varma, A.K. (2010). Optimized Hydrophobic Interactions and Hydrogen Bonding at the Target\u2013Ligand Interface Leads the Pathways of Drug Designing. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0012029"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4066","DOI":"10.1021\/acs.jmedchem.5b00104","article-title":"pkCSM: Predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures","volume":"58","author":"Pires","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2615","DOI":"10.1021\/jm020017n","article-title":"Molecular properties that influence the oral bioavailability of drug candidates","volume":"45","author":"Veber","year":"2002","journal-title":"J. Med. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(00)00129-0","article-title":"Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings","volume":"46","author":"Lipinski","year":"2001","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"728","DOI":"10.3109\/10408444.2010.494175","article-title":"A review of the electrophilic reaction chemistry involved in covalent DNA binding","volume":"40","author":"Enoch","year":"2010","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/0006-2952(61)90145-9","article-title":"A new and rapid colorimetric determination of acetylcholinesterase activity","volume":"7","author":"Ellman","year":"1961","journal-title":"Biochem. Pharmacol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2014A visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"105811","DOI":"10.1016\/j.arabjc.2024.105811","article-title":"Rapid Identification of Natural Acetylcholinesterase Inhibitors from Glycosmis parviflora Stem Utilizing Dereplication, In Vitro and In Silico Approach","volume":"17","author":"Duong","year":"2024","journal-title":"Arab. J. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1007\/s11030-024-10911-y","article-title":"Investigation of Cholinesterase and \u03b1-Glucosidase Enzyme Activities, and Molecular Docking and DFT Studies for 1,2-Disubstituted Cyclopentane Derivatives with Phenyl and Benzyl Units","volume":"29","author":"Taslimi","year":"2025","journal-title":"Mol. Divers."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2778","DOI":"10.1021\/ci200227u","article-title":"LigPlot+: Multiple ligand\u2013protein interaction diagrams for drug discovery","volume":"51","author":"Laskowski","year":"2011","journal-title":"J. Chem. Inf. Model."},{"key":"ref_60","unstructured":"Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., Scalmani, G., Barone, V., Mennucci, B., and Petersson, G.A. (2009). Gaussian 09, Revision D.01, Gaussian, Inc."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s00214-007-0310-x","article-title":"The M06 suite of density functionals for main-group thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition elements: Two new functionals and systematic testing of four M06-class functionals and 12 other functionals","volume":"120","author":"Zhao","year":"2008","journal-title":"Theor. Chem. Acc."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers","volume":"1","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3257","DOI":"10.1021\/ct300400x","article-title":"Optimization of the additive CHARMM all-atom protein force field targeting improved sampling of backbone \u03c6, \u03c8 and side-chain \u03c71 and \u03c72 dihedral angles","volume":"8","author":"Best","year":"2012","journal-title":"J. Chem. Theory Comput."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/7\/1113\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T08:09:32Z","timestamp":1774944572000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/7\/1113"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,27]]},"references-count":63,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["molecules31071113"],"URL":"https:\/\/doi.org\/10.3390\/molecules31071113","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,27]]}}}