Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

In silico Exploration of Bioactive Phytochemicals Against Neurodegenerative Diseases Via Inhibition of Cholinesterases

Author(s): Fawzi Mahomoodally*, Hassan H. Abdallah, Shanoo Suroowan, Sharmeen Jugreet, Yansheng Zhang and Xuebo Hu

Volume 26, Issue 33, 2020

Page: [4151 - 4162] Pages: 12

DOI: 10.2174/1381612826666200316125517

Price: $65

Abstract

Neurodegenerative disorders are estimated to become the second leading cause of death worldwide by 2040. Despite the widespread use of diverse allopathic drugs, these brain-associated disorders can only be partially addressed and long term treatment is often linked with dependency and other unwanted side effects. Nature, believed to be an arsenal of remedies for any illness, presents an interesting avenue for the development of novel neuroprotective agents. Interestingly, inhibition of cholinesterases, involved in the breakdown of acetylcholine in the synaptic cleft, has been proposed to be neuroprotective. This review therefore aims to provide additional insight via docking studies of previously studied compounds that have shown potent activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in vitro. Indeed, the determination of potent plant-based ligands for this purpose through in silico methods enables the elimination of lengthy and costly traditional methods of drug discovery. Herein, a literature search was conducted to identify active phytochemicals which are cholinesterase inhibitors. Following which in silico docking methods were applied to obtain docking scores. Compound structures were extracted from online ZINC database and optimized using AM1 implemented in gaussian09 software. Noteworthy ligands against AChE highlighted in this study include: 19,20-dihydroervahanine A and 19, 20-dihydrotabernamine. Regarding BChE inhibition, the best ligands were found to be 8-Clavandurylkaempferol, Na-methylepipachysamine D; ebeiedinone; and dictyophlebine. Thus, ligand optimization between such phytochemicals and cholinesterases coupled with in vitro, in vivo studies and randomized clinical trials can lead to the development of novel drugs against neurodegenerative disorders.

Keywords: Neuroprotective, docking, optimization, drug discovery, in vitro, in vivo.

« Previous Next »
[1]
Kumar GP, Anilakumar KR, Naveen S. Phytochemicals Having Neuroprotective Properties from Dietary Sources and Medicinal Herbs. Phcog J 2015; 7(1)
[http://dx.doi.org/10.5530/pj.2015.1.1]
[2]
Makhouri FR, Ghasemi JB. In Silico Studies in Drug Research Against Neurodegenerative Diseases. Curr Neuropharmacol 2018; 16(6): 664-725.
[http://dx.doi.org/10.2174/1570159X15666170823095628] [PMID: 28831921]
[3]
Ansari J, Siraj A, Inamdar N. Pharmacotherapeutic approaches of Parkinson’s disease. Int J Pharmacol 2010; 6(5): 584-90.
[http://dx.doi.org/10.3923/ijp.2010.584.590]
[4]
Adewusi EA, Moodley N, Steenkamp V. Medicinal plants with cholinesterase inhibitory activity: a review. Afr J Biotechnol 2010; 9(49): 8257-76.
[5]
Rasool M, Malik A, Qureshi MS, et al. Recent updates in the treatment of neurodegenerative disorders using natural compounds eCAM 2014; 2014
[6]
Citron M. Strategies for disease modification in Alzheimer’s disease. Nat Rev Neurosci 2004; 5(9): 677-85.
[http://dx.doi.org/10.1038/nrn1495] [PMID: 15322526]
[7]
Ahmad W, Ahmad B, Ahmad M, et al. In vitro inhibition of acetylcholinesterase, butyrylcholinesterase and lipoxygenase by crude extract of Myricaria elegans Royle. J Biol Sci 2003; 11: 1046-9.
[8]
Geula C, Darvesh S. Butyrylcholinesterase, cholinergic neurotransmission and the pathology of Alzheimer’s disease. Drugs Today (Barc) 2004; 40(8): 711-21.
[http://dx.doi.org/10.1358/dot.2004.40.8.850473] [PMID: 15510242]
[9]
Grill JD, Cummings JL. Novel targets for Alzheimer’s disease treatment. Expert Rev Neurother 2010; 10(5): 711.
[http://dx.doi.org/10.1586/ern.10.29] [PMID: 20420492]
[10]
US National Institutes of Health - National Institute on Aging. Alzheimer’s Disease Education & Referral (ADEAR) Center NIH Publication 2008.Available at http://www.nia.nih.gov/Alzheimers/
[11]
Bhatnagar M. Novel leads from herbal drugs for neurodegenerative diseases Herbal drugs: Ethnomedicine to modern medicine. Berlin, Heidelberg: Springer 2009; pp. 221-38.
[http://dx.doi.org/10.1007/978-3-540-79116-4_14]
[12]
Raina P, Santaguida P, Ismaila A, et al. Effectiveness of cholinesterase inhibitors and memantine for treating dementia: evidence review for a clinical practice guideline. Ann Intern Med 2008; 148(5): 379-97.
[http://dx.doi.org/10.7326/0003-4819-148-5-200803040-00009] [PMID: 18316756]
[13]
Kennedy DO, Wake G, Savelev S, et al. Modulation of mood and cognitive performance following acute administration of single doses of Melissa officinalis (Lemon balm) with human CNS nicotinic and muscarinic receptor-binding properties. Neuropsychopharmacology 2003; 28(10): 1871-81.
[http://dx.doi.org/10.1038/sj.npp.1300230] [PMID: 12888775]
[14]
Ballard CG, O’Brien JT, Reichelt K, et al. Aromatherapy as a safe and effective treatment for the management of agitation in severe dementia: the results of a double-blind, placebo-controlled trial with Melissa. J Clin Psychiatry 2002; 63(7): 553-8.
[http://dx.doi.org/10.4088/JCP.v63n0703] [PMID: 12143909]
[15]
Wake G, Court J, Pickering A, et al. CNS acetylcholine receptor activity in European medicinal plants traditionally used to improve failing memory. J Ethnopharmacol 2000; 69(2): 105-14.
[http://dx.doi.org/10.1016/S0378-8741(99)00113-0] [PMID: 10687867]
[16]
Kennedy DO, Scholey AB, Tildesley NT, et al. Modulation of mood and cognitive performance following acute administration of Melissa officinalis (lemon balm). Pharmacol Biochem Behav 2002; 72(4): 953-64.
[http://dx.doi.org/10.1016/S0091-3057(02)00777-3] [PMID: 12062586]
[17]
Olga P, Eleni K, Konstantinos C. Essential oils and neurodegenerative diseases: current data and future perspectives. Curr Top Nutraceutical Res 2012; 10(2): 123.
[18]
Amat-Ur-Rasool H, Ahmed M, Ahmed M. Designing second generation anti-Alzheimer compounds as inhibitors of human acetylcholinesterase: computational screening of synthetic molecules and dietary phytochemicals. PLoS One 2015; 10(9)e0136509
[http://dx.doi.org/10.1371/journal.pone.0136509] [PMID: 26325402]
[19]
Scotti L, Scotti MT, Scotti L, et al. Editorial: In Silico Studies in Drug Research Against Neurodegenerative Diseases. Curr Neuropharmacol 2018; 16(6): 647-8.
[http://dx.doi.org/10.2174/1570159X1606180608103840] [PMID: 29938615]
[20]
Scotti L, Tullius Scotti M, de Oliveira Lima E, et al. Experimental methodologies and evaluations of computer-aided drug design methodologies applied to a series of 2-aminothiophene derivatives with antifungal activities. Molecules 2012; 17(3): 2298-315.
[http://dx.doi.org/10.3390/molecules17032298] [PMID: 22367025]
[21]
Scotti L, Scotti MT, Ishiki HM, et al. Quantitative elucidation of the structure-bitterness relationship of cynaropicrin and grosheimin derivatives. Food Chem 2007; 105(1): 77-83.
[http://dx.doi.org/10.1016/j.foodchem.2007.03.038]
[22]
Scotti L, Fernandes MB, Muramatsu E, et al. Self-organizing maps and VolSurf approach to predict aldose reductase inhibition by flavonoid compounds. Rev Bras Farmacogn 2011; 21(1): 170-80.
[http://dx.doi.org/10.1590/S0102-695X2011005000028]
[23]
Adewusi EA, Moodley N, Steenkamp V. Antioxidant and acetylcholinesterase inhibitory activity of selected southern African medicinal plants. S Afr J Bot 2011; 77(3): 638-44.
[http://dx.doi.org/10.1016/j.sajb.2010.12.009]
[24]
Felder CC, Bymaster FP, Ward J, et al. Therapeutic opportunities for muscarinic receptors in the central nervous system. J Med Chem 2000; 43(23): 4333-53.
[http://dx.doi.org/10.1021/jm990607u] [PMID: 11087557]
[25]
Zhu X, Raina AK, Lee HG, Casadesus G, Smith MA, Perry G. Oxidative stress signalling in Alzheimer’s disease. Brain Res 2004; 1000(1-2): 32-9.
[http://dx.doi.org/10.1016/j.brainres.2004.01.012] [PMID: 15053949]
[26]
Dhiman P, Malik N, Khatkar A. 3D-QSAR and in-silico studies of natural products and related derivatives as monoamine oxidase inhibitors. Curr Neuropharmacol 2018; 16(6): 881-900.
[http://dx.doi.org/10.2174/1570159X15666171128143650] [PMID: 29189167]
[27]
Correa MF, Dos Santos Fernandes JP, Paulo J. Qsar modeling of histamine H3R antagonists/inverse agonists as future drugs for neurodegenerative diseases. Curr Neuropharmacol 2018; 16(6): 749-57.
[http://dx.doi.org/10.2174/1570159X15666170818100644] [PMID: 28820054]
[28]
Augen J. The evolving role of information technology in the drug discovery process. Drug Discov Today 2002; 7(5): 315-23.
[http://dx.doi.org/10.1016/S1359-6446(02)02173-6] [PMID: 11854055]
[29]
Ballard CG, Greig NH, Guillozet-Bongaarts AL, Enz A, Darvesh S. Cholinesterases: roles in the brain during health and disease. Curr Alzheimer Res 2005; 2(3): 307-18.
[http://dx.doi.org/10.2174/1567205054367838] [PMID: 15974896]
[30]
Xu Y, Colletier JP, Jiang H, et al. Induced-fit or preexisting equilibrium dynamics? Lessons from protein crystallography and MD simulations on acetylcholinesterase and implications for structure-based drug design. Protein Sci 2008; 17(4): 601-5.
[http://dx.doi.org/10.1110/ps.083453808] [PMID: 18359854]
[31]
Massoulié J, Pezzementi L, Bon S, et al. Molecular and cellular biology of cholinesterases. Prog Neurobiol 1993; 41(1): 31-91.
[http://dx.doi.org/10.1016/0301-0082(93)90040-Y] [PMID: 8321908]
[32]
Taylor P, Radić Z. The cholinesterases: from genes to proteins. Annu Rev Pharmacol Toxicol 1994; 34(1): 281-320.
[http://dx.doi.org/10.1146/annurev.pa.34.040194.001433] [PMID: 8042853]
[33]
Silman I, Sussman JL. Acetylcholinesterase: ‘classical’ and ‘non-classical’ functions and pharmacology. Curr Opin Pharmacol 2005; 5(3): 293-302.
[http://dx.doi.org/10.1016/j.coph.2005.01.014] [PMID: 15907917]
[34]
Nachon F, Nicolet Y, Masson P. [Butyrylcholinesterase: 3D structure, catalytic mechanisms Ann Pharm Fr 2005; 63(3): 194-206.
[http://dx.doi.org/10.1016/S0003-4509(05)82274-6] [PMID: 15976688]
[35]
Correa-Basurto J, Flores-Sandoval C, Marín-Cruz J, et al. Docking and quantum mechanic studies on cholinesterases and their inhibitors. Eur J Med Chem 2007; 42(1): 10-9.
[http://dx.doi.org/10.1016/j.ejmech.2006.08.015] [PMID: 17055616]
[36]
Lindner A, Schalke B, Toyka KV. Outcome in juvenile-onset myasthenia gravis: a retrospective study with long-term follow-up of 79 patients. J Neurol 1997; 244(8): 515-20.
[http://dx.doi.org/10.1007/s004150050135] [PMID: 9309559]
[37]
Tõugu V, Kesvatera T. Comparison of salt effects on the reactions of acetylcholinesterase with cationic and anionic inhibitors. Biochim Biophys Acta 2001; 1544(1-2): 189-95.
[http://dx.doi.org/10.1016/S0167-4838(00)00218-1] [PMID: 11341928]
[38]
Schwarz M, Glick D, Loewenstein Y, et al. Engineering of human cholinesterases explains and predicts diverse consequences of administration of various drugs and poisons. Pharmacol Ther 1995; 67(2): 283-322.
[http://dx.doi.org/10.1016/0163-7258(95)00019-D] [PMID: 7494866]
[39]
Schwarz M, Loewenstein-Lichtenstein Y, Glick D, et al. Successive organophosphate inhibition and oxime reactivation reveals distinct responses of recombinant human cholinesterase variants. Brain Res Mol Brain Res 1995; 31(1-2): 101-10.
[http://dx.doi.org/10.1016/0169-328X(95)00040-Y] [PMID: 7476018]
[40]
Ehret MJ, Chamberlin KW. Current practices in the treatment of alzheimer disease: where is the evidence after the phase iii trials? Clin Ther 2015; 37(8): 1604-16.
[http://dx.doi.org/10.1016/j.clinthera.2015.05.510] [PMID: 26122885]
[41]
Anand R, Gill KD, Mahdi AA. Therapeutics of Alzheimer’s disease: Past, present and future. Neuropharmacology 2014; 76(Pt A): 27-50.
[http://dx.doi.org/10.1016/j.neuropharm.2013.07.004] [PMID: 23891641]
[42]
Schneider LS, Mangialasche F, Andreasen N, et al. Clinical trials and late-stage drug development for Alzheimer’s disease: an appraisal from 1984 to 2014. J Intern Med 2014; 275(3): 251-83.
[http://dx.doi.org/10.1111/joim.12191] [PMID: 24605808]
[43]
Bhakta HK, Park CH, Yokozawa T, et al. Potential anti-cholinesterase and β-site amyloid precursor protein cleaving enzyme 1 inhibitory activities of cornuside and gallotannins from Cornus officinalis fruits. Arch Pharm Res 2017; 40(7): 836-53.
[http://dx.doi.org/10.1007/s12272-017-0924-z] [PMID: 28589255]
[44]
Ciro A, Park J, Burkhard G, et al. Biochemical differentiation of cholinesterases from normal and Alzheimer’s disease cortex. Curr Alzheimer Res 2012; 9(1): 138-43.
[http://dx.doi.org/10.2174/156720512799015127] [PMID: 21244353]
[45]
Li B, Stribley JA, Ticu A, et al. Abundant tissue butyrylcholinesterase and its possible function in the acetylcholinesterase knockout mouse. J Neurochem 2000; 75(3): 1320-31.
[http://dx.doi.org/10.1046/j.1471-4159.2000.751320.x] [PMID: 10936216]
[46]
Perry EK. The cholinergic system in old age and Alzheimer’s disease. Age Ageing 1980; 9(1): 1-8.
[http://dx.doi.org/10.1093/ageing/9.1.1] [PMID: 7361631]
[47]
Darvesh S, Hopkins DA, Geula C. Neurobiology of butyrylcholinesterase. Nat Rev Neurosci 2003; 4(2): 131-8.
[http://dx.doi.org/10.1038/nrn1035] [PMID: 12563284]
[48]
Mesulam MM, Guillozet A, Shaw P, et al. Acetylcholinesterase knockouts establish central cholinergic pathways and can use butyrylcholinesterase to hydrolyze acetylcholine. Neuroscience 2002; 110(4): 627-39.
[http://dx.doi.org/10.1016/S0306-4522(01)00613-3] [PMID: 11934471]
[49]
Inestrosa NC, Alvarez A, Perez CA, et al. Acetylcholinesterase accelerates assembly of amyloid-β-peptides into Alzheimer's fibrils: possible role of the peripheral site of the enzyme. Neuron 1996; 1; 16(4): 881-91.
[http://dx.doi.org/10.1016/S0896-6273(00)80108-7]
[50]
Das UN. Acetylcholinesterase and butyrylcholinesterase as possible markers of low-grade systemic inflammation. Med Sci Monit 2007; 13(12): RA214-21.
[PMID: 18049445]
[51]
Sussman JL, Harel M, Frolow F, et al. Atomic structure of acetylcholinesterase from Torpedo californica: a prototypic acetylcholine-binding protein. Science 1991; 253(5022): 872-9.
[http://dx.doi.org/10.1126/science.1678899] [PMID: 1678899]
[52]
Ordentlich A, Barak D, Kronman C, et al. Dissection of the human acetylcholinesterase active center determinants of substrate specificity. Identification of residues constituting the anionic site, the hydrophobic site, and the acyl pocket. J Biol Chem 1993; 268(23): 17083-95.
[PMID: 8349597]
[53]
Radić Z, Pickering NA, Vellom DC, et al. Three distinct domains in the cholinesterase molecule confer selectivity for acetyl- and butyrylcholinesterase inhibitors. Biochemistry 1993; 32(45): 12074-84.
[http://dx.doi.org/10.1021/bi00096a018] [PMID: 8218285]
[54]
Carvajal FJ, Inestrosa NC. Interactions of AChE with Aβ aggregates in Alzheimer’s brain: therapeutic relevance of IDN 5706. Front Mol Neurosci 2011; 4: 19.
[http://dx.doi.org/10.3389/fnmol.2011.00019] [PMID: 21949501]
[55]
Viayna E, Sabate R, Muñoz-Torrero D. Dual inhibitors of β-amyloid aggregation and acetylcholinesterase as multi-target anti-Alzheimer drug candidates. Curr Top Med Chem 2013; 13(15): 1820-42.
[http://dx.doi.org/10.2174/15680266113139990139] [PMID: 23931440]
[56]
Rosini M, Simoni E, Minarini A, et al. Multi-target design strategies in the context of Alzheimer’s disease: acetylcholinesterase inhibition and NMDA receptor antagonism as the driving forces. Neurochem Res 2014; 39(10): 1914-23.
[http://dx.doi.org/10.1007/s11064-014-1250-1] [PMID: 24493627]
[57]
Greenblatt HM, Guillou C, Guénard D, et al. The complex of a bivalent derivative of galanthamine with torpedo acetylcholinesterase displays drastic deformation of the active-site gorge: implications for structure-based drug design. J Am Chem Soc 2004; 126(47): 15405-11.
[http://dx.doi.org/10.1021/ja0466154] [PMID: 15563167]
[58]
Camps P, Formosa X, Galdeano C, et al. Novel donepezil-based inhibitors of acetyl- and butyrylcholinesterase and acetylcholinesterase-induced β-amyloid aggregation. J Med Chem 2008; 51(12): 3588-98.
[http://dx.doi.org/10.1021/jm8001313] [PMID: 18517184]
[59]
Jia P, Sheng R, Zhang J, et al. Design, synthesis and evaluation of galanthamine derivatives as acetylcholinesterase inhibitors. Eur J Med Chem 2009; 44(2): 772-84.
[http://dx.doi.org/10.1016/j.ejmech.2008.04.018] [PMID: 18550228]
[60]
Bartolucci C, Haller LA, Jordis U, et al. Probing Torpedo californica acetylcholinesterase catalytic gorge with two novel bis-functional galanthamine derivatives. J Med Chem 2010; 53(2): 745-51.
[http://dx.doi.org/10.1021/jm901296p] [PMID: 20025280]
[61]
Kozurkova M, Hamulakova S, Gazova Z, et al. Neuroactive multifunctional tacrine congeners with cholinesterase, anti-amyloid aggregation and neuroprotective properties. Pharmaceuticals 2011; 4(2): 382-418.
[http://dx.doi.org/10.3390/ph4020382]
[62]
Scherzer-Attali R, Pellarin R, Convertino M, et al. Complete phenotypic recovery of an Alzheimer’s disease model by a quinone-tryptophan hybrid aggregation inhibitor. PLoS One 2010; 5(6)e11101
[http://dx.doi.org/10.1371/journal.pone.0011101] [PMID: 20559435]
[63]
Bolea I, Juárez-Jiménez J, de Los Ríos C, et al. Synthesis, biological evaluation, and molecular modeling of donepezil and N-[(5-(benzyloxy)-1-methyl-1H-indol-2-yl)methyl]-N-methylprop-2-yn-1-amine hybrids as new multipotent cholinesterase/monoamine oxidase inhibitors for the treatment of Alzheimer’s disease. J Med Chem 2011; 54(24): 8251-70.
[http://dx.doi.org/10.1021/jm200853t] [PMID: 22023459]
[64]
Simoni E, Daniele S, Bottegoni G, et al. Combining galantamine and memantine in multitargeted, new chemical entities potentially useful in Alzheimer’s disease. J Med Chem 2012; 55(22): 9708-21.
[http://dx.doi.org/10.1021/jm3009458] [PMID: 23033965]
[65]
Bautista-Aguilera OM, Esteban G, Chioua M, et al. Multipotent cholinesterase/monoamine oxidase inhibitors for the treatment of Alzheimer’s disease: design, synthesis, biochemical evaluation, ADMET, molecular modeling, and QSAR analysis of novel donepezil-pyridyl hybrids. Drug Des Devel Ther 2014; 8: 1893-910.
[PMID: 25378907]
[66]
Wang L, Esteban G, Ojima M, et al. Donepezil + propargylamine + 8-hydroxyquinoline hybrids as new multifunctional metal-chelators, ChE and MAO inhibitors for the potential treatment of Alzheimer’s disease. Eur J Med Chem 2014; 80: 543-61.
[http://dx.doi.org/10.1016/j.ejmech.2014.04.078] [PMID: 24813882]
[67]
Nepovimova E, Uliassi E, Korabecny J, et al. Multitarget drug design strategy: quinone-tacrine hybrids designed to block amyloid-β aggregation and to exert anticholinesterase and antioxidant effects. J Med Chem 2014; 57(20): 8576-89.
[http://dx.doi.org/10.1021/jm5010804] [PMID: 25259726]
[68]
Korabecny J, Andrs M, Nepovimova E, et al. 7-Methoxytacrine-p-anisidine hybrids as novel dual binding site acetylcholinesterase inhibitors for Alzheimer’s disease treatment. Molecules 2015; 20(12): 22084-101.
[http://dx.doi.org/10.3390/molecules201219836] [PMID: 26690394]
[69]
Singh M, Kaur M, Chadha N, et al. Hybrids: a new paradigm to treat Alzheimer’s disease. Mol Divers 2016; 20(1): 271-97.
[http://dx.doi.org/10.1007/s11030-015-9628-9] [PMID: 26328942]
[70]
Piazzi L, Rampa A, Bisi A, et al. 3-(4-[[Benzyl(methyl)amino] methyl]phenyl)-6,7-dimethoxy-2H-2-chromenone (AP2238) inhibits both acetylcholinesterase and acetylcholinesterase-induced β-amyloid aggregation: a dual function lead for Alzheimer’s disease therapy. J Med Chem 2003; 46(12): 2279-82.
[http://dx.doi.org/10.1021/jm0340602] [PMID: 12773032]
[71]
Hernández-Rodríguez M, Correa-Basurto J, Martínez-Ramos F, et al. Design of multi-target compounds as AChE, BACE1, and amyloid-β(1-42) oligomerization inhibitors: in silico and in vitro studies. J Alzheimers Dis 2014; 41(4): 1073-85.
[http://dx.doi.org/10.3233/JAD-140471] [PMID: 24762947]
[72]
Guzior N, Bajda M, Skrok M, et al. Development of multifunctional, heterodimeric isoindoline-1,3-dione derivatives as cholinesterase and β-amyloid aggregation inhibitors with neuroprotective properties. Eur J Med Chem 2015; 92: 738-49.
[http://dx.doi.org/10.1016/j.ejmech.2015.01.027] [PMID: 25621991]
[73]
Meena P, Nemaysh V, Khatri M, et al. Synthesis, biological evaluation and molecular docking study of novel piperidine and piperazine derivatives as multi-targeted agents to treat Alzheimer’s disease. Bioorg Med Chem 2015; 23(5): 1135-48.
[http://dx.doi.org/10.1016/j.bmc.2014.12.057] [PMID: 25624107]
[74]
Basile L. Virtual screening in the search of new and potent anti-Alzheimer agentsComputational modeling of drugs against Alzheimer’s disease. New York, NY: Humana Press 2018; pp. 107-37.
[http://dx.doi.org/10.1007/978-1-4939-7404-7_4]
[75]
Khan RA, Bukhari IA, Nawaz SA, et al. Acetylcholinesterase and butyrylcholinesterase inhibitory potential of some Pakistani medicinal plants. J Basic Appl Sci 2006; 2: 07-10.
[76]
Bermudez-Lugo JA, Rosales-Hernandez MC, Deeb O, et al. In silico methods to assist drug developers in acetylcholinesterase inhibitor design. Curr Med Chem 2011; 18(9): 1241-8.
[77]
Ortiz JE, Pigni NB, Andujar SA, et al. Alkaloids from Hippeastrum argentinum and their cholinesterase-inhibitory activities: an in vitro and in silico study. J Nat Prod 2016; 79(5): 1241-8.
[http://dx.doi.org/10.1021/acs.jnatprod.5b00785] [PMID: 27096334]
[78]
Adhami HR, Linder T, Kaehlig H, et al. Catechol alkenyls from Semecarpus anacardium: acetylcholinesterase inhibition and binding mode predictions. J Ethnopharmacol 2012; 139(1): 142-8.
[http://dx.doi.org/10.1016/j.jep.2011.10.032] [PMID: 22075454]
[79]
Cortes N, Alvarez R, Osorio EH, et al. Alkaloid metabolite profiles by GC/MS and acetylcholinesterase inhibitory activities with binding-mode predictions of five Amaryllidaceae plants. J Pharm Biomed Anal 2015; 102: 222-8.
[http://dx.doi.org/10.1016/j.jpba.2014.09.022] [PMID: 25305596]
[80]
Castillo-Ordóñez WO, Tamarozzi ER, da Silva GM, et al. Exploration of the acetylcholinesterase inhibitory activity of some alkaloids from Amaryllidaceae family by molecular docking in silico. Neurochem Res 2017; 42(10): 2826-30.
[http://dx.doi.org/10.1007/s11064-017-2295-8] [PMID: 28497342]
[81]
da Silva VB, de Andrade P, Kawano DF, et al. In silico design and search for acetylcholinesterase inhibitors in Alzheimer’s disease with a suitable pharmacokinetic profile and low toxicity. Future Med Chem 2011; 3(8): 947-60.
[http://dx.doi.org/10.4155/fmc.11.67] [PMID: 21707398]
[82]
Adsersen A, Kjølbye A, Dall O, et al. Acetylcholinesterase and butyrylcholinesterase inhibitory compounds from Corydalis cava Schweigg. & Kort. J Ethnopharmacol 2007; 113(1): 179-82.
[http://dx.doi.org/10.1016/j.jep.2007.05.006] [PMID: 17574358]
[83]
Bhattacharjee P, Chakraborty S. Neurotransmitters in Edible Plants: Implications in Human HealthNeurotransmitters in Plants: Perspectives and Applications CRC Press 2019; 387-407.
[84]
Chlebek J, Macáková K, Cahlíková L, et al. Acetylcholinesterase and butyrylcholinesterase inhibitory compounds from Corydalis cava (Fumariaceae). Nat Prod Commun 2011; 6(5)
[85]
Chlebek J, Korábečný J, Doležal R, et al. In Vitro and In Silico Acetylcholinesterase Inhibitory Activity of Thalictricavine and Canadine and Their Predicted Penetration across the Blood-Brain Barrier. Molecules 2019; 24(7): 1340.
[http://dx.doi.org/10.3390/molecules24071340] [PMID: 30959739]
[86]
Muehlbacher M, Spitzer GM, Liedl KR, et al. Qualitative prediction of blood-brain barrier permeability on a large and refined dataset. J Comput Aided Mol Des 2011; 25(12): 1095-106.
[http://dx.doi.org/10.1007/s10822-011-9478-1] [PMID: 22109848]
[87]
Jeyam MU, Karthika GR, Poornima VA, et al. Molecular understanding and in silico validation of traditional medicines for Parkinson’s disease. AJPCR 2012; 5(4): 125-8.
[88]
Bagchi P, Kar A, Vinobha CS. Establishing an in-silico ayurvedic medication towards treatment of Schizophrenia. Int J Syst Biol 2009; 1(2): 46.
[89]
Lee S, Youn K, Lim G, et al. In Silico Docking and In Vitro Approaches towards BACE1 and Cholinesterases Inhibitory Effect of Citrus Flavanones. Molecules 2018; 23(7): 1509.
[http://dx.doi.org/10.3390/molecules23071509] [PMID: 29932100]
[90]
Pathak A, Madar IH, Raithatha K, et al. In-Silico Identification of Potential Inhibitors Against AChE Using Cheminformatics Approach. MOJ Proteomics Bioinform 2014; 1(4): 00022.
[91]
Irwin JJ, Sterling T, Mysinger MM, et al. ZINC: a free tool to discover chemistry for biology. J Chem Inf Model 2012; 52(7): 1757-68.
[http://dx.doi.org/10.1021/ci3001277] [PMID: 22587354]
[92]
Frisch MJ, Trucks GW, Schlegel HB, et al. Gaussian 09 Revision D 01, 2009. Wallingford, CT: Gaussian Inc. 2009; p. 93.
[93]
Cheung J, Rudolph MJ, Burshteyn F, et al. Structures of human acetylcholinesterase in complex with pharmacologically important ligands. J Med Chem 2012; 55(22): 10282-6.
[http://dx.doi.org/10.1021/jm300871x] [PMID: 23035744]
[94]
Hoffmann M, Stiller C, Endres E, et al. Highly Selective Butyrylcholinesterase Inhibitors with Tunable Duration of Action by Chemical Modification of Transferable Carbamate Units Exhibit Pronounced Neuroprotective Effect in an Alzheimer’s Disease Mouse Model. J Med Chem 2019; 62(20): 9116-40.
[http://dx.doi.org/10.1021/acs.jmedchem.9b01012] [PMID: 31609115]
[95]
Nicolet Y, Lockridge O, Masson P, et al. Crystal structure of human butyrylcholinesterase and of its complexes with substrate and products. J Biol Chem 2003; 278(42): 41141-7.
[http://dx.doi.org/10.1074/jbc.M210241200] [PMID: 12869558]
[96]
The Molinspiration Database. Available at:. www.molinspi ration.com
[97]
Shafferman A, Kronman C, Flashner Y, et al. Mutagenesis of human acetylcholinesterase. Identification of residues involved in catalytic activity and in polypeptide folding. J Biol Chem 1992; 267(25): 17640-8.
[PMID: 1517212]
[98]
Sharma J, Ramanathan K, Sethumadhavan R. Identification of potential inhibitors against acetylcholinesterase associated with Alzheimer’s diseases: a molecular docking approach. JCMMD 2011; 1(1): 44-51.
[99]
Rollinger JM, Schuster D, Baier E, et al. Taspine: bioactivity-guided isolation and molecular ligand-target insight of a potent acetylcholinesterase inhibitor from Magnolia x soulangiana. J Nat Prod 2006; 69(9): 1341-6.
[http://dx.doi.org/10.1021/np060268p] [PMID: 16989531]
[100]
Zhu Y, Peng L, Hu J, et al. Current anti-Alzheimer’s disease effect of natural products and their principal targets. J Integr Neurosci 2019; 18(3): 327-39.
[http://dx.doi.org/10.31083/j.jin.2019.03.1105] [PMID: 31601083]
[101]
Pereira DM, Ferreres F, Oliveira JM, et al. Pharmacological effects of Catharanthus roseus root alkaloids in acetylcholinesterase inhibition and cholinergic neurotransmission. Phytomedicine 2010; 17(8-9): 646-52.
[http://dx.doi.org/10.1016/j.phymed.2009.10.008] [PMID: 19962870]
[102]
Ingkaninan K, Changwijit K, Suwanborirux K. Vobasinyl-iboga bisindole alkaloids, potent acetylcholinesterase inhibitors from Tabernaemontana divaricata root. J Pharm Pharmacol 2006; 58(6): 847-52.
[http://dx.doi.org/10.1211/jpp.58.6.0015] [PMID: 16734986]
[103]
Berkov S, Codina C, Viladomat F, et al. N-Alkylated galanthamine derivatives: Potent acetylcholinesterase inhibitors from Leucojum aestivum. Bioorg Med Chem Lett 2008; 18(7): 2263-6.
[http://dx.doi.org/10.1016/j.bmcl.2008.03.008] [PMID: 18356045]
[104]
Ahmed E, Nawaz SA, Malik A, et al. Isolation and cholinesterase-inhibition studies of sterols from Haloxylon recurvum. Bioorg Med Chem Lett 2006; 16(3): 573-80.
[http://dx.doi.org/10.1016/j.bmcl.2005.10.042] [PMID: 16274989]
[105]
Awang K, Chan G, Litaudon M, et al. 4-Phenylcoumarins from Mesua elegans with acetylcholinesterase inhibitory activity. Bioorg Med Chem 2010; 18(22): 7873-7.
[http://dx.doi.org/10.1016/j.bmc.2010.09.044] [PMID: 20943395]
[106]
Ata A, Iverson CD, Kalhari KS, et al. Triterpenoidal alkaloids from Buxus hyrcana and their enzyme inhibitory, anti-fungal and anti-leishmanial activities. Phytochemistry 2010; 71(14-15): 1780-6.
[http://dx.doi.org/10.1016/j.phytochem.2010.06.017] [PMID: 20655557]
[107]
Lin BQ, Ji H, Li P, et al. Inhibitors of acetylcholine esterase in vitro-screening of steroidal alkaloids from Fritillaria species. Planta Med 2006; 72(9): 814-8.
[http://dx.doi.org/10.1055/s-2006-947168] [PMID: 16881015]
[108]
Jung HA, Jin SE, Park JS, et al. Antidiabetic complications and anti-Alzheimer activities of sophoflavescenol, a prenylated flavonol from Sophora flavescens, and its structure-activity relationship. Phytother Res 2011; 25(5): 709-15.
[http://dx.doi.org/10.1002/ptr.3326] [PMID: 21077260]
[109]
Sancheti S, Um BH, Seo SY. 1, 2, 3, 4, 6-penta-O-galloyl-β-D-glucose: A cholinesterase inhibitor from Terminalia chebula. S Afr J Bot 2010; 76(2): 285-8.
[http://dx.doi.org/10.1016/j.sajb.2009.11.006]
[110]
Devkota KP, Lenta BN, Wansi JD, et al. Bioactive 5α-pregnane-type steroidal alkaloids from Sarcococca hookeriana. J Nat Prod 2008; 71(8): 1481-4.
[http://dx.doi.org/10.1021/np800305b] [PMID: 18681480]
[111]
Ahmed F, Chandra JN, Urooj A, et al. In vitro antioxidant and anticholinesterase activity of Acorus calamus and Nardostachys jatamansi rhizomes. J Pharm Res 2009; 2: 830-3.
[112]
Das A, Shanker G, Nath C, et al. A comparative study in rodents of standardized extracts of Bacopa monniera and Ginkgo biloba: anticholinesterase and cognitive enhancing activities. Pharmacol Biochem Behav 2002; 73(4): 893-900.
[http://dx.doi.org/10.1016/S0091-3057(02)00940-1] [PMID: 12213536]
[113]
Abdul Manap AS, Vijayabalan S, Madhavan P, et al. Bacopa monnieri, a Neuroprotective Lead in Alzheimer disease: a review on its properties, mechanisms of action, and preclinical and clinical studies. Drug Target Insights 2019; 131177392819866412
[http://dx.doi.org/10.1177/1177392819866412] [PMID: 31391778]
[114]
Ali SK, Hamed AR, Soltan MM, et al. In-vitro evaluation of selected Egyptian traditional herbal medicines for treatment of Alzheimer disease. BMC Complement Altern Med 2013; 13(1): 121.
[http://dx.doi.org/10.1186/1472-6882-13-121] [PMID: 23721591]
[115]
Mahdy K, Shaker O, Wafay H, et al. Effect of some medicinal plant extracts on the oxidative stress status in Alzheimer’s disease induced in rats. Eur Rev Med Pharmacol Sci 2012; 16(3)(Suppl. 3): 31-42.
[PMID: 22957416]
[116]
Siqueira IR, Fochesatto C, da Silva AL, et al. Ptychopetalum olacoides, a traditional Amazonian “nerve tonic”, possesses anticholinesterase activity. Pharmacol Biochem Behav 2003; 75(3): 645-50.
[http://dx.doi.org/10.1016/S0091-3057(03)00113-8] [PMID: 12895682]
[117]
Ren Y, Houghton PJ, Hider RC, et al. Novel diterpenoid acetylcholinesterase inhibitors from Salvia miltiorhiza. Planta Med 2004; 70(3): 201-4.
[http://dx.doi.org/10.1055/s-2004-815535] [PMID: 15114495]
[118]
Lu Y, Foo LY. Antioxidant activities of polyphenols from sage (Salvia officinalis). Food Chem 2001; 75(2): 197-202.
[http://dx.doi.org/10.1016/S0308-8146(01)00198-4]
[119]
Orhan I, Kartal M, Naz Q, et al. Antioxidant and anticholinesterase evaluation of selected Turkish Salvia species. Food Chem 2007; 103(4): 1247-54.
[http://dx.doi.org/10.1016/j.foodchem.2006.10.030]
[120]
Chattipakorn S, Pongpanparadorn A, Pratchayasakul W, et al. Tabernaemontana divaricata extract inhibits neuronal acetylcholinesterase activity in rats. J Ethnopharmacol 2007; 110(1): 61-8.
[http://dx.doi.org/10.1016/j.jep.2006.09.007] [PMID: 17023131]
[121]
Al-Snafi AE, Talab TA, Majid WJ. Medicinal plants with central nervous activity-An overview (Part 1). IOSR J Pharm 2019; 9(3): 52-102.

Rights & Permissions Print Cite
Article Metrics
8
© 2024 Bentham Science Publishers | Privacy Policy