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Current Pharmaceutical Design

Editor-in-Chief

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

Research Article

Ajmalicine and its Analogues Against AChE and BuChE for the Management of Alzheimer’s Disease: An In-silico Study

Author(s): Shu Liu, Minyan Dang, Yan Lei, Syed S. Ahmad, Mohammad Khalid, Mohammad A. Kamal and Li Chen*

Volume 26 , Issue 37 , 2020

Page: [4808 - 4814] Pages: 7

DOI: 10.2174/1381612826666200407161842

Price: $65

Abstract

Background: Alzheimer's disease (AD) is the most well-known reason for disability in persons aged greater than 65 years worldwide. AD influences the part of the brain that controls cognitive and non-cognitive functions.

Objective: The study focuses on the screening of natural compounds for the inhibition of AChE and BuChE using a computational methodology.

Methods: We performed a docking-based virtual screening utilizing the 3D structure of AChE and BuChE to search for potential inhibitors for AD. In this work, a screened inhibitor Ajmalicine similarity search was carried out against a natural products database (Super Natural II). Lipinski rule of five was carried out and docking studies were performed between ligands and enzyme using ‘Autodock4.2’.

Results: Two phytochemical compounds SN00288228 and SN00226692 were predicted for the inhibition of AChE and BuChE, respectively. The docking results revealed Ajmalicine, a prominent natural alkaloid, showing promising inhibitory potential against AChE and BuChE with the binding energy of -9.02 and -8.89 kcal/mole, respectively. However, SN00288228- AChE, and SN00226692-BuChE were found to have binding energy -9.88 and -9.54 kcal/mole, respectively. These selected phytochemical compounds showed better interactions in comparison to Ajmalicine with the target molecule.

Conclusion: The current study verifies that SN00288228 and SN00226692 are more capable inhibitors of human AChE and BuChE as compared to Ajmalicine with reference to ΔG values.

Keywords: Alzheimer's disease, AChE, BuChE, ajmalicine, binding energy, inhibition constant.

[1]
Huang WJ, Zhang X, Chen WW. Role of oxidative stress in Alzheimer’s disease. Biomed Rep 2016; 4(5): 519-22.
[http://dx.doi.org/10.3892/br.2016.630] [PMID: 27123241]
[2]
Ahmad SS, Khan H. Danish Rizvi SM, Ansari SA, Ullah R, Rastrelli L, Mahmood HM, Siddiqui MH. Computational Study of Natural Compounds for the Clearance of Amyloid-Beta: A Potential Therapeutic Management Strategy for Alzheimer’s Disease. Molecules 2019; 24(18): 3233.
[http://dx.doi.org/10.3390/molecules24183233] [PMID: 31491967]
[3]
Hebert LE, Weuve J, Scherr PA, Evans DA. Alzheimer disease in the United States (2010-2050) estimated using the 2010 census. Neurology 2013; 80(19): 1778-83.
[http://dx.doi.org/10.1212/WNL.0b013e31828726f5] [PMID: 29385058]
[4]
Young SC. A Systematic Review of Antiamyloidogenic and Metal-Chelating Peptoids: Two Structural Motifs for the Treatment of Alzheimer’s Disease. Molecules 2018; 23(2): 296.
[http://dx.doi.org/10.3390/molecules23020296] [PMID: 29385058]
[5]
Islam MR, Zaman A, Jahan I, Chakravorty R, Chakraborty S. In silico QSAR analysis of quercetin reveals its potential as therapeutic drug for Alzheimer’s disease. J Young Pharm 2013; 5(4): 173-9.
[http://dx.doi.org/10.1016/j.jyp.2013.11.005] [PMID: 24563598]
[6]
Butters N, Delis DC, Lucas JA. Clinical assessment of memory disorders in amnesia and dementia. Annu Rev Psychol 1995; 46: 493-523.
[http://dx.doi.org/10.1146/annurev.ps.46.020195.002425] [PMID: 7872736]
[7]
Zesiewicz TA, Strom JA, Borenstein AR, et al. Heart failure in Parkinson’s disease: analysis of the United States medicare current beneficiary survey. Parkinsonism Relat Disord 2004; 10(7): 417-20.
[http://dx.doi.org/10.1016/j.parkreldis.2004.04.001] [PMID: 15465398]
[8]
Ahmad SS, Akhtar S. Screening and Elucidation of Selected Natural Compounds for Anti- Alzheimer’s Potential Targeting BACE-1 Enzyme: A Case Computational Study. Curr Comput Aided Drug Des 2017; 13(4): 311-8.
[http://dx.doi.org/10.2174/1573409913666170414123825] [PMID: 28413992]
[9]
Gupta S, Mohan CG. Dual binding site and selective acetylcholinesterase inhibitors derived from integrated pharmacophore models and sequential virtual screening. BioMed Res Int 2014; 2014291214
[http://dx.doi.org/10.1155/2014/291214] [PMID: 25050335]
[10]
Ahmad SS, Akhtar S, Jamal QM, et al. Multiple Targets for the Management of Alzheimer’s Disease. CNS Neurol Disord Drug Targets 2016; 15(10): 1279-89.
[http://dx.doi.org/10.2174/1871527315666161003165855] [PMID: 27712576]
[11]
Howland RH. Alternative drug therapies for dementia. J Psychosoc Nurs Ment Health Serv 2011; 49(5): 17-20.
[http://dx.doi.org/10.3928/02793695-20110407-03] [PMID: 21553703]
[12]
Muñoz-Delgado E, Montenegro MF, Campoy FJ, et al. Expression of cholinesterases in human kidney and its variation in renal cell carcinoma types. FEBS J 2010; 277(21): 4519-29.
[http://dx.doi.org/10.1111/j.1742-4658.2010.07861.x] [PMID: 20883446]
[13]
Goodsell DS, Morris GM, Olson AJ. Automated docking of flexible ligands: applications of AutoDock. J Mol Recognit 1996; 9(1): 1-5.
[http://dx.doi.org/10.1002/(SICI)1099-1352(199601)9:1<1::AID-JMR241>3.0.CO;2-6] [PMID: 8723313]
[14]
Inestrosa NC, Alarcón R. Molecular interactions of acetylcholinesterase with senile plaques. J Physiol Paris 1998; 92(5-6): 341-4.
[http://dx.doi.org/10.1016/S0928-4257(99)80002-3] [PMID: 16572227]
[15]
Houghton PJ, Ren Y, Howes MJ. Acetylcholinesterase inhibitors from plants and fungi. Nat Prod Rep 2006; 23(2): 181-99.
[http://dx.doi.org/10.1039/b508966m] [PMID: 16572227]
[16]
Summers WK, Majovski LV, Marsh GM, Tachiki K, Kling A. Oral tetrahydroaminoacridine in long-term treatment of senile dementia, Alzheimer type. N Engl J Med 1986; 315(20): 1241-5.
[http://dx.doi.org/10.1056/NEJM198611133152001] [PMID: 2430180]
[17]
Greig NH, Utsuki T, Yu Q, et al. A new therapeutic target in Alzheimer’s disease treatment: attention to butyrylcholinesterase. Curr Med Res Opin 2001; 17(3): 159-65.
[http://dx.doi.org/10.1185/03007990152673800] [PMID: 11900310]
[18]
Ahmad SS, Waheed T, Rozeen S, Mahmood S, Kamal MA. Therapeutic Study of Phytochemicals Against Cancer and Alzheimer’s Disease Management. Curr Drug Metab 2020.
[http://dx.doi.org/10.2174/1389200221666200103092719] [PMID: 31902351]
[19]
Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 2001; 46(1-3): 3-26.
[http://dx.doi.org/10.1016/S0169-409X(00)00129-0] [PMID: 11259830]
[20]
Shaikh S, Ahmad SS, Ansari MA, et al. Prediction of comparative inhibition efficiency for a novel natural ligand, galangin against human brain acetylcholinesterase, butyrylcholinesterase and 5-lipoxygenase: a neuroinformatics study. CNS Neurol Disord Drug Targets 2014; 13(3): 452-9.
[http://dx.doi.org/10.2174/18715273113126660162] [PMID: 24059300]
[21]
Rehman A, Akhtar S, Siddiqui MH, et al. Identification of potential leads against 4-hydroxytetrahydrodipicolinate synthase from Mycobacterium tuberculosis. Bioinformation 2016; 12(11): 400-7.
[http://dx.doi.org/10.6026/97320630012400] [PMID: 28293071]
[22]
Sharma N, Akhtar S, Jamal QMS, et al. Elucidation of Antiangiogenic Potential of Vitexin Obtained from Cucumis sativus Targeting Hsp90 Protein: A Novel Multipathway Targeted Approach to Restrain Angiogenic Phenomena. Med Chem 2017; 13(3): 282-91.
[http://dx.doi.org/10.2174/1573406413666161111152720] [PMID: 27834134]
[23]
Srivastava M, Sharma S, Misra P. Elicitation Based Enhancement of Secondary Metabolites in Rauwolfia serpentina and Solanum khasianum Hairy Root Cultures. Pharmacogn Mag 2016; 12(Suppl. 3): S315-20.
[http://dx.doi.org/10.4103/0973-1296.185726] [PMID: 27563218]
[24]
Zenk MH, El-Shagi H, Arens H, et al. Formation of the Indole Alkaloids Serpentine and Ajmalicine in Cell Suspension Cultures of Catharanthus Roseus. Plant Tissue Culture and Its Bio-Technological Application 1977; pp. 27-43.
[http://dx.doi.org/10.1007/978-3-642-66646-9_3]
[25]
Ambrin G, Ahmad M, Alqarawi AA, Hashem A, Abd Allah EF, Ahmad A. Conversion of Cytochrome P450 2D6 of Human Into a FRET-Based Tool for Real-Time Monitoring of Ajmalicine in Living Cells. Front Bioeng Biotechnol 2019; 7: 375.
[http://dx.doi.org/10.3389/fbioe.2019.00375] [PMID: 31828069]
[26]
Alam A, Shaikh S, Ahmad SS, et al. Molecular interaction of human brain acetylcholinesterase with a natural inhibitor huperzine-B: an enzoinformatics approach. CNS Neurol Disord Drug Targets 2014; 13(3): 487-90.
[http://dx.doi.org/10.2174/18715273113126660163] [PMID: 24059299]
[27]
Chatonnet A, Lockridge O. Comparison of butyrylcholinesterase and acetylcholinesterase. Biochem J 1989; 260(3): 625-34.
[http://dx.doi.org/10.1042/bj2600625] [PMID: 2669736]
[28]
Dave KR, Syal AR, Katyare SS. Tissue cholinesterases. A comparative study of their kinetic properties. Z Natforsch C J Biosci 2000; 55(1-2): 100-8.
[http://dx.doi.org/10.1515/znc-2000-1-219] [PMID: 10739108]
[29]
Prody CA, Zevin-Sonkin D, Gnatt A, Goldberg O, Soreq H. Isolation and characterization of full-length cDNA clones coding for cholinesterase from fetal human tissues. Proc Natl Acad Sci USA 1987; 84(11): 3555-9.
[http://dx.doi.org/10.1073/pnas.84.11.3555] [PMID: 3035536]
[30]
Ahmad SS, Khalid M, Younis K. Interaction study of dietary fibers (pectin and cellulose) with meat proteins using bioinformatics analysis: An In-Silico study. LWT 2020; 119: 108889
[http://dx.doi.org/10.1016/j.lwt.2019.108889]

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