Molecular docking studies of a phytocompound kanzonol B as a potential acetylcholine esterase inhibitor for epilepsy
References
- V.L. Feigin, T. Vos, E. Nichols, M.O. Owolabi, W.M. Carroll, M. Dichgans, G. Deuschl, P. Parmar, M. Brainin, C. Murray, The global burden of neurological disorders: translating evidence into policy, Lancet Neurology 19 (2020) 255–265. DOI: 10.1016/S1474-4422(19)30411-9
- Y.A. Ismail, Y. Haitham, M. Walid, H. Mohamed, Y.M.A. El-Satar, Efficacy of acetylcholinesterase inhibitors on reducing hippocampal atrophy rate: a systematic review and meta-analysis, BMC Neurology 25 (2025) 60. DOI: 10.1186/s12883-024-03933-4
- L. Fan, R. Wang, Q. Zan, K. Zhao, Y. Zhang, Y. Huang, X. Yu, Y. Yang, W. Lu, S. Shuang, X. Yang, C. Dong, A near-infrared fluorescent probe for visualization of acetylcholinesterase flux in the acute epileptic mice brain, Chemical and Biomedical Imaging 3 (2025) 332–340. DOI: 10.1021/cbmi.4c00058
- P. Li, S. Liu, Q. Liu, J. Shen, R. Yang, B. Jiang, C. He, P. Xiao, Screening of acetylcholinesterase inhibitors and characterizing of phytochemical constituents from Dichocarpum auriculatum (Franch.) W.T. Wang & P. K. Hsiao through UPLC-MS combined with an acetylcholinesterase inhibition assay in vitro, Journal of Ethnopharmacology 245 (2019) 112185. DOI: 10.1016/j.jep.2019.112185
- J. Xie, H. Jiang, Y.H. Wan, A.Y. Du, K.J. Guo, T. Liu, W.Y. Ye, X. Niu, J. Wu, X.Q. Dong, X.J. Zhang, Induction of a 55 kDa acetylcholinesterase protein during apoptosis and its negative regulation by the Akt pathway, Journal of Molecular Cell Biology 3 (2011) 250-259. DOI: 10.1093/jmcb/mjq047
- X.J. Zhang, D.S. Greenberg, Acetylcholinesterase Involvement in Apoptosis, Frontiers in Molecular Neuroscience 5 (2012) 40. DOI: 10.3389/fnmol.2012.00040
- L.E. Paraoanu, P.G. Layer, Acetylcholinesterase in cell adhesion, neurite growth and network formation, The FEBS Journal 275 (2008) 618–624. DOI: 10.1111/j.1742-4658.2007.06237.x
- S. Ruangritchankul, P. Chantharit, S. Srisuma, L.C. Gray, Adverse drug reactions of acetylcholinesterase inhibitors in older people living with dementia: a comprehensive literature review, Therapeutics and Clinical Risk Management 17 (2021) 927–949. DOI: 10.2147/TCRM.S323387
- E. Kröger, M. Mouls, M. Wilchesky, M. Berkers, P.-H. Carmichael, R. van Marum, P. Souverein, T. Egberts, M.L. Laroche, Adverse drug reactions reported with cholinesterase inhibitors: an analysis of 16 years of individual case safety reports from VigiBase, Annals of Pharmacotherapy 49 (2015) 1197–1206. DOI: 10.1177/1060028015602274
- C.C. Tan, J.T. Yu, H.F. Wang, M.S. Tan, X.F. Meng, C. Wang, T. Jiang, X.C. Zhu, L. Tan, Efficacy and safety of donepezil, galantamine, rivastigmine, and memantine for the treatment of Alzheimer’s disease: a systematic review and meta-analysis, Journal of Alzheimers Disease JAD 41 (2014) 615–631. DOI: 10.3233/JAD-132690
- T.B. Ali, T.R. Schleret, B.M. Reilly, W.Y. Chen, R. Abagyan, Adverse effects of cholinesterase inhibitors in dementia, according to the pharmacovigilance databases of the United States and Canada, PLOS One 10 (2015) e0144337. DOI: 10.1371/journal.pone.0144337
- D.L. Bai, X.C. Tang, X.C. He, Huperzine A, a potential therapeutic agent for the treatment of Alzheimer’s disease, Current Medicinal Chemistry 7 (2000) 355–374. DOI: 10.2174/0929867003375281
- R. Gersner, D. Ekstein, S.C. Dhamne, S.C. Schachter, A. Rotenberg, Huperzine a prophylaxis against pentylenetetrazole-induced seizures in rats is associated with increased cortical inhibition, Epilepsy Research 117 (2015) 97–103. DOI: 10.1016/j. eplepsyres.2015.08.012
- A. Mishra, R.K. Goel, Adjuvant anticholinesterase therapy for the management of epilepsy-induced memory deficit: a critical pre-clinical study, Basic Clinical Pharmacology Toxicology 115 (2014) 512–517. DOI: 10.1111/bcpt.12275
- E. Rębas, Role of flavonoids in protecting against neurodegenerative diseases possible mechanisms of action, International Journal of Molecular Science 26 (2025) 4763. DOI: 10.3390/ijms26104763
- T. Minocha, H. Birla, A.A. Obaid, V. Rai, P. Sushma, C. Shivamallu, M. Moustafa, M. Al-Shehri, A. Al-Emam, M.A. Tikhonova, S.K. Yadav, B. Poeggeler, D. Singh, S.K. Singh, Flavonoids as promising neuroprotectants and their therapeutic potential against Alzheimer’s disease, Oxidative Medicine and Cellular Longevity 2022 (2022) 6038996. DOI: 10.1155/2022/6038996
- M. Ramezani, A.Z. Meymand, F. Khodagholi, H.M. Kamsorkh, E. Asadi, M. Noori, K. Rahimian, A.S. Shahrbabaki, A. Talebi, H. Parsaiyan, S. Shiravand, N. Darbandi, A role for flavonoids in the prevention and/or treatment of cognitive dysfunction, learning, and memory deficits: a review of preclinical and clinical studies, Nutritional Neuroscience 26 (2023) 156–172. DOI: 10.1080/1028415X.2022.2028058
- M.S. Uddin, M.T. Kabir, K. Niaz, P. Jeandet, C. Clément, B. Mathew, A. Rauf, K.R.R. Rengasamy, E. Sobarzo-Sánchez, G.M. Ashraf, L. Aleya, Molecular insight into the therapeutic promise of flavonoids against Alzheimer’s disease, Molecules 25 (2020) 1267. DOI: 10.3390/molecules25061267
- T. Fukai, J. Nishizawa, T. Nomura, Five isoprenoid-substituted flavonoids from Glycyrrhiza eurycarpa, Phytochemistry 35 (1994) 515–519. DOI: 10.1016/S0031-9422(00)94793-9
- J.R. Fan, Y. Kuang, Z.Y. Dong, Y. Yi, Y.X. Zhou, B. Li, X. Qiao, M. Ye, Prenylated phenolic compounds from the aerial parts of Glycyrrhiza uralensis as PTP1B and α-glucosidase inhibitors, Journal of Natural Products 83 (2020) 814–824. DOI: 10.1021/acs.jnatprod.9b00262
- L.J. Siang, K. Vijeepallam, A. Muthuraman, P. Pavadai, T. Karunakaran, V. Ravichandran, Exploration of Canarium odontophyllum fruit phytoconstituents as potential candidates against epilepsy using in silico studies. Journal of Genetic Engineering and Biotechnology 23 (2025) 100561. DOI: 10.1016/j.jgeb.2025.100561
- D.H. Kim, H. Li, Y.E. Han, J.H. Jeong, H.J. Lee, J.H. Ryu, Modulation of inducible nitric oxide synthase expression in LPS-stimulated BV-2 microglia by prenylated chalcones from Cullen corylifolium (L.) Medik. through inhibition of I-κBα degradation, Molecules 23 (2018) 109. DOI: 10.3390/molecules23010109
- M.N. Arthur, K. Bebla, E. Broni, C. Ashley, M. Velazquez, X. Hua, R. Radhakrishnan, S.K. Kwofie, W.A. Miller, Design of inhibitors that target the Menin-Mixed-Lineage leukemia interaction, Computation 12 (2024) 3. DOI: 10.3390/computation12010003
- T.P. Saliu, H.I. Umar, O.J. Ogunsile, M.O. Okpara, N. Yanaka, O.O. Elekofehinti, Molecular docking and pharmacokinetic studies of phytocompounds from Nigerian Medicinal Plants as promising inhibitory agents against SARS-CoV-2 methyltransferase (nsp16), Journal of Genetic Engineering and Biotechnology 19 (202AD) 172. DOI: 10.1186/s43141-021-00273-5
- R. Veerasamy, R. Seenivasan, H. Rajak, P. Pavadai, P. Thangavelu, Mushroom-derived compounds unveiled naringin as a potential multi-targeted anti-breast cancer compound -an in-silico approach, Journal of Faculty of Pharmacy of Ankara University 49 (2025) 21–41. DOI: 10.33483/jfpau.1512113
- W.R. Mir, B.A. Bhat, M.A. Rather, S. Muzamil, A. Almilaibary, M. Alkhanani, M.A. Mir, Molecular docking analysis and evaluation of the antimicrobial properties of the constituents of Geranium wallichianum D. Don ex Sweet from Kashmir Himalaya, Scientific Report 12 (2022) 12547. DOI: 10.1038/s41598-022-16102-9
- R. Dharavath, M. Sarasija, K.N. Prathima, M. Ram Reddy, S. Panga, V. Thumma, D. Ashok, Microwave-assisted synthesis of (6-((1-(4-aminophenyl)-1H-1,2,3-triazol-4-yl)methoxy)substituted benzofuran-2-yl)(phenyl)methanones, evaluation of in vitro anticancer, antimicrobial activities and molecular docking on COVID-19, Results in Chemistry 4 (2022) 100628. DOI: 10.1016/j.rechem.2022.100628
- L. El Mchichi, A. El Aissouq, R. Kasmi, A. Belhassan, R. El-Mernissi, A. Ouammou, T. Lakhlifi, M. Bouachrine, In silico design of novel pyrazole derivatives containing thiourea skeleton as anti-cancer agents using: 3D QSAR, Drug-Likeness studies, ADMET prediction and molecular docking, Materials Today: Proceedings 45 (2021) 7661–7674. DOI: 10.1016/j.matpr.2021.03.152
- B. Asrar, N. Ali, I. Ali, M. Naveed, In silico investigation of ketamine and methylphenidate drug-drug conjugate for MDD and ADHD treatment using MD simulations and MMGBSA, Scientific Reports 15 (2025) 24565. DOI: 10.1038/s41598-024-82302-0
- N. Misuan, S. Mohamad, T. Tubiana, M.K.K. Yap, Ensemble-based molecular docking and spectrofluorometric analysis of interaction between cytotoxin and tumor necrosis factor receptor 1, Journal of Biomolecular Structure and Dynamics 41 (2023) 15339–15353. DOI: 10.1080/07391102.2023.2188945
- K. Petsri, M. Yokoya, S. Tungsukruthai, T. Rungrotmongkol, B. Nutho, C. Vinayanuwattikun, N. Saito, T. Matsubara, R. Sato, P. Chanvorachote, Structure–activity relationships and molecular docking analysis of Mcl-1 targeting renieramycin T analogues in patient-derived lung cancer cells, Cancers 12 (2020) 875. DOI: 10.3390/cancers12040875
- N.T. Tran, I. Jakovlić, W.M. Wang, In silico characterisation, homology modelling and structure-based functional annotation of blunt snout bream (Megalobrama amblycephala) Hsp70 and Hsc70 proteins, Journal of Animal Science and Technology 57 (2015) 44. DOI: 10.1186/s40781-015-0077-x
- C. Colovos, T.O. Yeates, Verification of protein structures: Patterns of nonbonded atomic interactions, Protein Science 2 (1993) 1511–1519. DOI: 10.1002/pro.5560020916
- A. Elengoe, M.A. Naser, S. Hamdan, Modeling and docking studies on novel mutants (K71L and T204V) of the ATPase domain of human heat shock 70 kDa protein 1, International Journal of Molecular Sciences 15 (2014) 6797–6814. DOI: 10.3390/ijms15046797
- R.A. Laskowski, M.W. MacArthur, D.S. Moss, J.M. Thornton, PROCHECK: a program to check the stereochemical quality of protein structures, Journal of Applied Crystallography 26 (1993) 283–291. DOI: 10.1107/S0021889892009944
- M. Wiederstein, M.J. Sippl, ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins, Nucleic Acids Research 35 (2007) W407–W410. DOI: 10.1093/nar/gkm290
- M. Mohanty, P.S. Mohanty, Molecular docking in organic, inorganic, and hybrid systems: a tutorial review, Monatshefte Chemistry 154 (2023) 683–707. DOI: 10.1007/s00706-023-03076-1
- M.R.F. Pratama, H. Poerwono, S. Siswodihardjo, Introducing a two‐dimensional graph of docking score difference vs. similarity of ligand‐receptor interactions, Indonesian Journal of Biotechnology 26 (2021) 54–60. DOI: 10.22146/ijbiotech.62194
- D. Ramírez, J. Caballero, Is it reliable to take the molecular docking top scoring position as the best solution without considering available structural data?, Molecules 23 (2018) 1038. DOI: 10.3390/molecules23051038
- M.J. Alves, H.J.C. Froufe, A.F.T. Costa, A.F. Santos, L.G. Oliveira, S.R.M. Osório, R.M.V. Abreu, M. Pintado, I.C.F.R. Ferreira, Docking studies in target proteins involved in antibacterial action mechanisms: extending the knowledge on standard antibiotics to antimicrobial mushroom compounds, Molecules 19 (2014) 1672–1684. DOI: 10.3390/molecules19021672
- D.R. Houston, M.D. Walkinshaw, Consensus docking: improving the reliability of docking in a virtual screening context, Journal of Chemical Information and Modeling 53 (2013) 384–390. DOI: 10.1021/ci300399w
- B. Divya, J. Narayanan, V. Chitra, T. Tamilanban, Evaluation of anti-convulsant activity of olivetol on PTZ-induced seizure model, Neuroquantology 20 (2022) 372–80.
- G. Ahmad, N. Rasool, K. Rizwan, I. Imran, A.F. Zahoor, M. Zubair, Synthesis, in-vitro cholinesterase inhibition, in-vivo anticonvulsant activity and in-silico exploration of N-(4-methylpyridin-2-yl)thiophene-2-carboxamide analogs, Bioorganic Chemistry 92 (2019) 103216.
- S. Bon, M. Vigny, J. Massoulié, Asymmetric and globular forms of acetylcholinesterase in mammals and birds, Proceedings of the National Academy of Sciences 76 (1979) 2546–2550. DOI: 10.1073/pnas.76.6.2546
- S. Abubakar, B.K. Khor, K.Y. Khaw, V. Murugaiyah, K.L. Chan, Cholinesterase inhibitory potential of Dillenia suffruticosa chemical constituents and protective effect against Aβ−induced toxicity in transgenic Caenorhabditis elegans model, Phytomedicine Plus 1 (2021) 100022. DOI: 10.1016/j.phyplu.2021.100022
- R.T. Feunaing, J.A. Gbaweng Yaya, J.N. Nyemb, N.I. Bassigue, H.L. Ketsemen, C. Henoumont, A.K. Kandeda, A. Venditti, S. Laurent, E. Talla, Antiradical and anti-acethylcholinesterase constituents from the methylene chloride extract of Ganoderma applanatum (Pers.) Pat (Ganodermataceae) and molecular docking study, Natural Product Research (2025) 1–13. DOI: 10.1080/14786419.2025.2491113
- V.B.S.C. Thunuguntla, C.S. B, K.K. B, B. Js, Screening and in silico analysis of Hyptis suaveolens metabolites for acetylcholinesterase inhibition, Asian Journal of Pharmaceutical and Clinical Research 9 (2016) 148–153.
- F. Ur-Rehman, M.F. Khan, I. Khan, R. Roohullah, Molecular interactions of an alkaloid euchrestifoline as a new acetylcholinesterase inhibitor, Bangladesh Journal of Pharmacology 8 (2013) 361–364.
- J.L. Sussman, M. Harel, F. Frolow, C. Oefner, A. Goldman, L. Toker, I. Silman, Atomic structure of acetylcholinesterase from Torpedo californica : a prototypic acetylcholine-binding protein, Science 253 (1991) 872–879. DOI: 10.1126/science.1678899
- L. Pezzementi, F. Nachon, A. Chatonnet, Evolution of acetylcholinesterase and butyrylcholinesterase in the vertebrates: an atypical butyrylcholinesterase from the Medaka Oryzias latipes, PLOS One 6 (2011) e17396. DOI: 10.1371/journal.pone.0017396
- C. Seniya, G.J. Khan, K. Uchadia, Identification of potential herbal inhibitor of acetylcholinesterase associated Alzheimer’s disorders using molecular docking and molecular dynamics simulation, Biochemistry Research International 2014 (2014) 705451. DOI: 10.1155/2014/705451
- M. Bajda, A. Więckowska, M. Hebda, N. Guzior, C.A. Sotriffer, B. Malawska, Structure-based search for new inhibitors of cholinesterases, International Journal of Molecular Sciences 14 (2013) 5608. DOI: 10.3390/ijms14035608
- Z.Y. Ibrahim, Gideon Adamu Shallangwa, A. Uzairu, S.E. Abechi, Molecular docking, drug-likeness and SwissADME evaluations of the interactions of 2’-substituted Triclosan derivatives with Plasmodium falciparum Enoyl-Acyl carrier protein reductase, Malaysian Journal of Pharmaceutical Sciences 20 (2022) 51–64. DOI: 10.21315/mjps2022.20.2.5
- C.A. Lipinski, Lead- and drug-like compounds: the rule-of-five revolution, Drug Discovery Today: Technologies 1 (2004) 337–341. DOI: 10.1016/j.ddtec.2004.11.007
- C.A. Lipinski, F. Lombardo, B.W. Dominy, P.J. Feeney, Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings1, Advanced Drug Delivery Reviews 46 (2001) 3–26. DOI: 10.1016/S0169-409X(00)00129-0
- M.P. Pollastri, Overview on the rule of five, Current Protocols in Pharmacology 49 (2010) 9.12.1-9.12.8. DOI: 10.1002/0471141755.ph0912s49
- D.F. Veber, S.R. Johnson, H.Y. Cheng, B.R. Smith, K.W. Ward, K.D. Kopple, Molecular properties that influence the oral bioavailability of drug candidates, Journal of Medicinal Chemistry 45 (2002) 2615–2623. DOI: 10.1021/jm020017n
- X. Ma, C. Chen, J. Yang, Predictive model of blood-brain barrier penetration of organic compounds, Acta Pharmacologica Sinica 26 (2005) 500–512. DOI: 10.1111/j.1745-7254.2005.00068.x
- S. Kunwittaya, C. Nantasenamat, L. Treeratanapiboon, A. Srisarin, C. Isarankura-Na-Ayudhya, V. Prachayasittikul, Influence of logBB cut-off on the prediction of blood-brain barrier permeability, Biomedical and Applied Technology Journal 1 (2013) 16-34.
- J. Bojarska, M. Remko, M. Breza, I.D. Madura, K. Kaczmarek, J. Zabrocki, W.M. Wolf, A supramolecular approach to structure-based design with a focus on synthons hierarchy in ornithine-derived ligands: Review, synthesis, experimental and in silico studies, Molecules 25 (2020) 1135. DOI: 10.3390/molecules25051135
- Y.C. Martin, A bioavailability score, Journal of Medicinal Chemistry 48 (2005) 3164–3170. DOI: 10.1021/jm0492002
- E. Stavropoulou, G.G. Pircalabioru, E. Bezirtzoglou, The role of cytochromes P450 in infection, Frontiers in Immunology 9 (2018) 89. DOI: 10.3389/fimmu.2018.00089
- A. Coin, M.V. Pamio, C. Alexopoulos, S. Granziera, F. Groppa, G. de Rosa, A. Girardi, G. Sergi, E. Manzato, R. Padrini, Donepezil plasma concentrations, CYP2D6 and CYP3A4 phenotypes, and cognitive outcome in Alzheimer’s disease, European Journal of Clinical Pharmacology 72 (2016) 711–717. DOI: 10.1007/s00228-016-2033-1
- P.J. Tiseo, S.L. Rogers, L.T. Friedhoff, Pharmacokinetic and pharmacodynamic profile of donepezil HCl following evening administration, British Journal of Clinical Pharmacology 46 (1998) 13–18. DOI: 10.1046/j.1365-2125.1998.0460s1013.x
- A. Daina, V. Zoete, A BOILED-Egg to predict gastrointestinal absorption and brain penetration of small molecules, ChemMedChem 11 (2016) 1117–1121. DOI: 10.1002/cmdc.201600182
- F. Zafar, A. Gupta, K. Thangavel, K. Khatana, A.A. Sani, A. Ghosal, P. Tandon, N. Nishat, Physicochemical and pharmacokinetic analysis of anacardic acid derivatives, ACS Omega 5 (2020) 6021−6030. DOI: 10.1021/acsomega.9b04398
- F. Darusman, T. Rusdiana, I. Sopyan, H. Rahma, M. Hanifa, Recent progress in pharmaceutical excipients as P-glycoprotein inhibitors for potential improvement of oral drug bioavailability: A comprehensive overview, Pharmacia 72 (2025) 1–16. DOI: 10.3897/pharmacia.72.e140734
Language: English
Page range: 120 - 131
Submitted on: Sep 1, 2025
Accepted on: Oct 10, 2025
Published on: Oct 29, 2025
Published by: Ovidius University of Constanta
In partnership with: Paradigm Publishing Services
Publication frequency: 2 times per year
Keywords:
Related subjects:
© 2025 Lim Joe Siang, Ravichandran Veerasamy, published by Ovidius University of Constanta
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.