• Punabaka Jyothi Department of Zoology, Sri Venkateswara University, Tirupati, Andhra Pradesh, India
  • Kuna Yellamma Department of Zoology, Sri Venkateswara University, Tirupati, Andhra Pradesh, India



Alzheimer`s disease (AD), Acetylcholinesterase, Butyrylcholinesterase, Lead Molecules


Objective: Alzheimer's disease (AD), a progressive neurodegenerative disorder with many cognitive and neuropsychiatric symptoms, is biochemically characterized by a significant decrease in the brain neurotransmitter Acetylcholine (ACh).Methods: In the present insilico study, six plant bioactive compounds namely Harmol, Vasicine, Harmaline, Harmine, Harmane and Harmalol (from P. Nigellastrum Bunge) were analyzed for their inhibitory role on AChE (Acetylcholinesterase) and BChE (Butyrylcholinesterase) activity by applying the molecular docking studies. Other parameters viz. determination of molecular interaction-based binding affinity values, protein-ligand interactions, Lipinski rule of five, functional properties and biological activities for the above compounds were also calculated by employing the appropriate bioinformatics tools.Results: The results of docking analysis clearly showed that Harmalol has highest binding affinity with AChE (-8.6 kcal/mole) and BChE (-8.0 kcal/mole) but it does not qualified the enzyme inhibitory activity, since it was exerted, and also has least percentage activity on AD and neurodegenerative disease. Whereas, the Harmine has been second qualified binding affinity (-8.4 kcal/mol) and first in other parameters when compared with Harmalol.Conclusion: Based on docking results and other parameters conducted, we are concluding that Harmine is the best compound for further studies to treat AD.Keywords: Alzheimer's disease (AD), Acetylcholinesterase, Butyrylcholinesterase, Lead Molecules


Download data is not yet available.


Tsalkovich L, Sallon S, Paavilainen H, Rosenmann H. Anti-alzheimer’s disease related activities of israeli medicinal plants. JSM Alzheimer’s Dis Related Dementia 2015;2:1015-22.

Chandra MP, Venkateshwar R. Biological evaluation of schiff bases of new isatin derivatives for anti-Alzheimer’s activity. Asian J Pharm Clin Res 2014;7:114-7.

Miroslav P. Cholinesterases, a target of pharmacology and toxicology. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2011;155:219–30.

Iskar M, Zeller G, Zhao XM, van NV, Bork P. Drug discovery in the age of systems biology: the rise of computational approaches for data integration. Curr Opin Biotechnol 2012;23:609–16.

Ortega SS, Cara LC, Salvador MK. In silico pharmacology for a multidisciplinary drug discovery process. Drug Metabol Drug Interact 2012;27:199–207.

Lu C, John KM, Hoang TT, Sharangdhar SP, Lei DC, Shuxing Z. From laptop to benchtop to bedside: structure-based drug design on protein targets. Curr Pharm Design 2012;18:1217-39.

Ting Zhao, Ke-min D, Lei Z, Xue-mei C, Chang-hong W, Zheng-tao W. Acetylcholinesterase and Butyrylcholinesterase inhibitory activities of ð›½-carboline and quinoline alkaloids derivatives from the plants of genus peganum. Hindawi Publishing Corporation J Chem 2013;2013:1-6.

Helen MB, John W, Zukang F, Gary G, Bhat TN, Helge W, et al. The protein data bank. Nucleic Acids Res 2000;28:235–42.

Allgardsson A, Berg L, Akfur C, Hörnberg A, Worek F, Linusson A, et al. Structureof a prereaction complex between the nerve agent sarin, its biological target acetylcholinesterase, and the antidote HI-6. Proc Natl Acad Sci 2016;113:5514-9.

Carletti E, Schopfer LM, Colletier JP, Froment MT, Nachon F, Weik M, et al. Reaction of cresyl saligenin phosphate, the organophosphorus agent implicated in aerotoxic syndrome, with human cholinesterases: mechanistic studies employing kinetics, mass spectrometry, and X-ray structure analysis. Chem Res Toxicol 2011;24:797-808.

Gajendran N, Aruldass I, Dhanapal S. In silico docking studies on the anti-cancer effect of thymoquinone on interaction with phosphatase and tensin homolog located on chromosome 10q23: a regulator of pi3k/akt pathway. Asian J Pharm Clin Res 2015;8:192-5.

Dallakyan S, Olson AJ. Small-molecule library screening by docking with PyRx. Methods Mol Biol 2015;1263:243-50.

Seeliger D, de Groot BL. Ligand docking and binding site analysis with PyMOL and Autodock/Vina. J Comput Aided Mol Des 2010;24:417–22.

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 Delivery Rev 2001;46:3–26.

Alexey L, Dmitrii F, Vladimir P. PASS: prediction of activity spectra for biologically active substances. Bioinformatics 2000;16:747-8.

Houghton PJ, Ren Y, Howes MJ. Acetylcholinesterase inhibitors from plants and fungi. Nat Prod Rep 2006;23:181-99.

Williams P, Sorribas A, Howes MJ. Natural Products as a source of Alzheimer’s drugs leads. Nat Prod Rep 2011;28:48-77.

Mukherjee PK, Kumar V, Mal M, Houghton PJ. Acetylcholinesterase inhibitors from plants. Phytomedicine 2007;14:289-300.

Arkypova VN, Dzyadevych SV, Soldatkin AP, El’skaya AV, Martelet C, Jaffrezic-RN. Development and optimisation of biosensors based on ph-sensitive field effect transistors and cholinesterases for sensitive detection of solanaceous glycoalkaloids. Biosens Bioelectron 2003;18:1047–53.

Dzyadevich S, Arkhypova VN, Soldatkin AP, Elskaya AV, Martelet C, Jaffrezic RN. Enzyme biosensor for tomatine detection in tomatoes. Anal Lett 2004;37:1611–24.

Benilova IV, Arkhypova VN, Dzyadeviych SV, Jaffrezic RN, Martelet C, Soldatkin AP. Kinetics of human and horse sera cholinesterases inhibition with solanaceous glycoalkaloids: study by potentiometric biosensor. Pestic Biochem Physiol 2006;86:203–10.

Miroslav Pohanka. Inhibitors of acetylcholinesterase and butyrylcholinesterase meet immunity. Int J Mol Sci 2014;15:9809–25.

Ekins S, Mestres J, Testa B. In silico pharmacology for drug discovery: methods for virtual ligand screening and profiling. Br J Pharmacol 2007;152:9–20.

Tracey B, Pedro C, Salim B, Richard G, Andrew JD, Jim W. Sites Identify: a protein functional site prediction tool. BMC Bioinformatics 2009;10:379-91.



How to Cite

Jyothi, P., and K. Yellamma. “MOLECULAR DOCKING STUDIES ON THE THERAPEUTIC TARGETS OF ALZHEIMER’S DISEASE (AChE AND BChE) USING NATURAL BIOACTIVE ALKALOIDS”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 8, no. 12, Dec. 2016, pp. 108-12, doi:10.22159/ijpps.2016v8i12.14833.



Original Article(s)