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Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry

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ISSN (Print): 1871-5230
ISSN (Online): 1875-614X

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Research Article

In-silico Prediction of the Beta-carboline Alkaloids Harmine and Harmaline as Potent Drug Candidates for the Treatment of Parkinson’s disease

Author(s): Rumpa Banerjee*, Mukesh Kumar, Isha Gaurav*, Sudha Thakur, Abhimanyu Thakur, Kunal Singh, Sanchari Karak, Rajeswar Das and Mohit Chhabra

Volume 20, Issue 3, 2021

Published on: 11 November, 2020

Page: [250 - 263] Pages: 14

DOI: 10.2174/1871523019999201111192344

Price: $65

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Abstract

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disease manifested by core symptoms of loss of motor control and postural instability. Loss of dopaminergic neurons is the cause of PD, thus enhancing dopamine level by pharmacological treatment is one of the key treatment strategies for PD. However, the limitations of current treatment strategies open the possibility of novel drug candidates for the treatment of PD.

Objective: To investigate the anti-PD potential of Harmine and Harmaline. We aim to evaluate the therapeutic potential of Harmine and Harmaline by in-silico approaches; molecular docking, pharmacokinetic and Prediction of Activity Spectra for Substances (PASS) analysis were used for evaluating the therapeutic potential of Harmine and Harmaline and standard drug levodopa (L-DOPA).

Methods: Auto dock vina was used for molecular docking of all three compounds against D2- and D3- dopamine receptors. The pharmacokinetics (PKs) and toxicity profile were predicted by pkCSM, and the pharmacological activity was predicted by PASS analysis.

Results: Molecular docking showed a higher binding affinity of Harmine and Harmaline as compared to L-DOPA, and these results were supported by in-silico pharmacokinetic and toxicity profiling. Moreover, PASS analysis showed anti-PD activity of Harmine and Harmaline.

Conclusion: Harmine and Harmaline exhibit higher binding affinity towards D2- and D3- dopamine receptors compared to L-DOPA, and PKs and toxicity profile support their potential as drug candidates for PD therapy.

Keywords: Anti-Parkinson's drug, neurodegenerative disease, neuroscience, pharmacology, molecular docking, toxicity profile.

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[1]
de Lau, L.M.L.; Breteler, M.M.B. Epidemiology of Parkinson’s disease. Lancet Neurol., 2006, 5(6), 525-535.
[http://dx.doi.org/10.1016/S1474-4422(06)70471-9] [PMID: 16713924]
[2]
Marras, C.; Chaudhuri, K.R. Nonmotor features of Parkinson’s disease subtypes. Mov. Disord., 2016, 31(8), 1095-1102.
[http://dx.doi.org/10.1002/mds.26510] [PMID: 26861861]
[3]
Greffard, S.; Verny, M.; Bonnet, A.M.; Beinis, J.Y.; Gallinari, C.; Meaume, S.; Piette, F.; Hauw, J.J.; Duyckaerts, C. Motor score of the Unified Parkinson Disease Rating Scale as a good predictor of Lewy body-associated neuronal loss in the substantia nigra. Arch. Neurol., 2006, 63(4), 584-588.
[http://dx.doi.org/10.1001/archneur.63.4.584] [PMID: 16606773]
[4]
Yang, P.; Perlmutter, J.S.; Benzinger, T.L.S.; Morris, J.C.; Xu, J. Dopamine D3 receptor: A neglected participant in Parkinson Disease pathogenesis and treatment? Ageing Res. Rev., 2020, 57, 100994.
[http://dx.doi.org/10.1016/j.arr.2019.100994] [PMID: 31765822]
[5]
Wang, S.; Che, T.; Levit, A.; Shoichet, B.K.; Wacker, D.; Roth, B.L. Structure of the D2 dopamine receptor bound to the atypical antipsychotic drug risperidone. Nature, 2018, 555(7695), 269-273.
[http://dx.doi.org/10.1038/nature25758] [PMID: 29466326]
[6]
Howard, C.D.; Li, H.; Geddes, C.E.; Jin, X. Dynamic Nigrostriatal Dopamine Biases Action Selection. Neuron, 2017, 93(6), 1436-1450.
[http://dx.doi.org/10.1016/j.neuron.2017.02.029] [PMID: 28285820]
[7]
Mercuri, N.B.; Bernardi, G. The ‘magic’ of L-dopa: why is it the gold standard Parkinson’s disease therapy? Trends Pharmacol. Sci., 2005, 26(7), 341-344.
[http://dx.doi.org/10.1016/j.tips.2005.05.002] [PMID: 15936832]
[8]
Aquino, C.C.; Fox, S.H. Clinical spectrum of levodopa-induced complications. Mov. Disord., 2015, 30(1), 80-89.
[http://dx.doi.org/10.1002/mds.26125] [PMID: 25488260]
[9]
Obeso, J.A.; Olanow, C.W.; Nutt, J.G.; Givup, G. Levodopa motor complications in Parkinson’s disease. Trends Neurosci., 2000, 23(10)(Suppl.), S2-S7.
[http://dx.doi.org/10.1016/S1471-1931(00)00031-8] [PMID: 11052214]
[10]
de la Fuente-Fernández, R.; Lidstone, S.; Stoessl, A.J. Placebo effect and dopamine release. J. Neural Transm. Suppl., 2006, (70), 415-418.
[PMID: 17017561]
[11]
Ogawa, N. Levodopa and dopamine agonists in the treatment of Parkinson’s disease: Advantages and disadvantages. Eur. Neurol., 1994, 34(Suppl. 3), 20-28.
[http://dx.doi.org/10.1159/000119538] [PMID: 7821332]
[12]
Su, D-F. Defining pharmacology of natural products in the 21st century - challenge on multiple fronts. Front. Pharmacol., 2010, 1, 5.
[http://dx.doi.org/10.3389/fphar.2010.00005] [PMID: 21607060]
[13]
Amit Koparde, A.; Chandrashekar Doijad, R.; Shripal Magdum, C. Natural Products in Drug Discovery. In: Pharmacognosy - Medicinal Plants; IntechOpen, 2019.
[http://dx.doi.org/10.5772/intechopen.82860]
[14]
Ekor, M. The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety. Front. Pharmacol., 2014, 4, 177.
[http://dx.doi.org/10.3389/fphar.2013.00177] [PMID: 24454289]
[15]
Callaway, J.C.; Brito, G.S.; Neves, E.S. Phytochemical analyses of Banisteriopsis caapi and Psychotria viridis. J. Psychoactive Drugs, 2005, 37(2), 145-150.
[http://dx.doi.org/10.1080/02791072.2005.10399795] [PMID: 16149327]
[16]
Favaro, V.M.; Yonamine, M.; Soares, J.C.K.; Oliveira, M.G.M. Effects of long-term ayahuasca administration on memory and anxiety in rats. PLoS One, 2015, 10(12), e0145840.
[http://dx.doi.org/10.1371/journal.pone.0145840] [PMID: 26716991]
[17]
Rodd, R. Snuff synergy: preparation, use and pharmacology of yopo and Banisteriopsis caapi among the Piaroa of southern Venezuela. J. Psychoactive Drugs, 2002, 34(3), 273-279.
[http://dx.doi.org/10.1080/02791072.2002.10399963] [PMID: 12422937]
[18]
Wang, Y.H.; Samoylenko, V.; Tekwani, B.L.; Khan, I.A.; Miller, L.S.; Chaurasiya, N.D.; Rahman, M.M.; Tripathi, L.M.; Khan, S.I.; Joshi, V.C.; Wigger, F.T.; Muhammad, I. Composition, standardization and chemical profiling of Banisteriopsis caapi, a plant for the treatment of neurodegenerative disorders relevant to Parkinson’s disease. J. Ethnopharmacol., 2010, 128(3), 662-671.
[http://dx.doi.org/10.1016/j.jep.2010.02.013] [PMID: 20219660]
[19]
Djamshidian, A.; Bernschneider-Reif, S.; Poewe, W.; Lees, A.J. Banisteriopsis caapi, a Forgotten Potential Therapy for Parkinson’s Disease? Mov. Disord. Clin. Pract. (Hoboken), 2015, 3(1), 19-26.
[http://dx.doi.org/10.1002/mdc3.12242] [PMID: 30713897]
[20]
Samoylenko, V.; Rahman, M.M.; Tekwani, B.L.; Tripathi, L.M.; Wang, Y-H.; Khan, S.I.; Khan, I.A.; Miller, L.S.; Joshi, V.C.; Muhammad, I. Banisteriopsis caapi, a unique combination of MAO inhibitory and antioxidative constituents for the activities relevant to neurodegenerative disorders and Parkinson’s disease. J. Ethnopharmacol., 2010, 127(2), 357-367.
[http://dx.doi.org/10.1016/j.jep.2009.10.030] [PMID: 19879939]
[21]
Santos, R.G.; Landeira-Fernandez, J.; Strassman, R.J.; Motta, V.; Cruz, A.P.M. Effects of ayahuasca on psychometric measures of anxiety, panic-like and hopelessness in Santo Daime members. J. Ethnopharmacol., 2007, 112(3), 507-513.
[http://dx.doi.org/10.1016/j.jep.2007.04.012] [PMID: 17532158]
[22]
Phillips, M.A.; Stewart, M.A.; Woodling, D.L.; Xie, Z-R. Has Molecular Docking Ever Brought us a Medicine?Molecular Docking; InTech, 2018.
[http://dx.doi.org/10.5772/intechopen.72898]
[23]
Lengauer, T.; Rarey, M. Computational methods for biomolecular docking. Curr. Opin. Struct. Biol., 1996, 6(3), 402-406.
[http://dx.doi.org/10.1016/S0959-440X(96)80061-3] [PMID: 8804827]
[24]
Kitchen, D.B.; Decornez, H.; Furr, J.R.; Bajorath, J. Docking and scoring in virtual screening for drug discovery: Methods and applications. Nat. Rev. Drug Discov., 2004, 3(11), 935-949.
[http://dx.doi.org/10.1038/nrd1549] [PMID: 15520816]
[25]
Trott, O.; Olson, A.J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem., 2010, 31(2), 455-461.
[PMID: 19499576]
[26]
Gaurav, I.; Singh, T.; Thakur, A.; Kumar, G.; Rathee, P.; Kumari, P.; Sweta, K. Synthesis, in-vitro and in-silico evaluation of Silver Nanoparticles with Root Extract of Withania somnifera for antibacterial activity via binding of penicillin binding protein-4. Curr. Pharm. Biotechnol., 2020, 21(15), 1674-1687.
[http://dx.doi.org/10.2174/1389201021666200702152000] [PMID: 32614743]
[27]
Morris, G.M.; Huey, R.; Lindstrom, W.; Sanner, M.F.; Belew, R.K.; Goodsell, D.S.; Olson, A.J. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J. Comput. Chem., 2009, 30(16), 2785-2791.
[http://dx.doi.org/10.1002/jcc.21256] [PMID: 19399780]
[28]
Hanwell, MD; Curtis, DE; Lonie, DC; Vandermeersch, T; Zurek, E; Hutchison, GR Avogadro: An advanced semantic chemical editor, visualization, and analysis platform. J. Cheminformatics, 2012, 4, 1-17.
[29]
Pettersen, E.F.; Goddard, T.D.; Huang, C.C.; Couch, G.S.; Greenblatt, D.M.; Meng, E.C.; Ferrin, T.E. UCSF Chimera-A visualization system for exploratory research and analysis. J. Comput. Chem., 2004, 25(13), 1605-1612.
[http://dx.doi.org/10.1002/jcc.20084] [PMID: 15264254]
[30]
Schrödinger, LLC The PyMOL molecular graphics system. Version 18, 2015.
[31]
Biovia, DSJSDDS Discovery studio modeling environment; , 2017.
[32]
Banerjee, P.; Eckert, A.O.; Schrey, A.K.; Preissner, R. ProTox-II: A webserver for the prediction of toxicity of chemicals. Nucleic Acids Res., 2018, 46(W1), W257-W263.
[http://dx.doi.org/10.1093/nar/gky318] [PMID: 29718510]
[33]
Pires, D.E.V.; Blundell, T.L.; Ascher, D.B. pkCSM: Predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. J. Med. Chem., 2015, 58(9), 4066-4072.
[http://dx.doi.org/10.1021/acs.jmedchem.5b00104] [PMID: 25860834]
[34]
Daina, A.; Michielin, O.; Zoete, V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep., 2017, 7, 42717.
[http://dx.doi.org/10.1038/srep42717] [PMID: 28256516]
[35]
Venugopal, V.C.; Thakur, A.; Chennabasappa, L.K.; Mishra, G.; Singh, K.; Rathee, P.; Ranjan, A. Phycocyanin Extracted from Oscillatoria minima Shows Antimicrobial, Algicidal, and Antiradical Activities: In silico and in vitro analysis. Antiinflamm. Antiallergy Agents Med. Chem., 2020, 19(3), 240-253.
[http://dx.doi.org/10.2174/1871523018666190405114524] [PMID: 30950358]
[36]
Daina, A.; Zoete, V. A boiled-egg to predict gastrointestinal absorption and brain penetration of small molecules. ChemMedChem, 2016, 11(11), 1117-1121.
[http://dx.doi.org/10.1002/cmdc.201600182] [PMID: 27218427]
[37]
Parasuraman, S. Prediction of activity spectra for substances. J. Pharmacol. Pharmacother., 2011, 2(1), 52-53.
[http://dx.doi.org/10.4103/0976-500X.77119] [PMID: 21701651]
[38]
Singh, S.P.; Nongalleima, K.; Singh, N.I.; Doley, P.; Singh, C.B.; Singh, T.R.; Sahoo, D. Zerumbone reduces proliferation of HCT116 colon cancer cells by inhibition of TNF-alpha. Sci. Rep., 2018, 8(1), 4090.
[http://dx.doi.org/10.1038/s41598-018-22362-1] [PMID: 29511228]
[39]
Gfeller, D.; Michielin, O.; Zoete, V. Shaping the interaction landscape of bioactive molecules. Bioinformatics, 2013, 29(23), 3073-3079.
[http://dx.doi.org/10.1093/bioinformatics/btt540] [PMID: 24048355]
[40]
Fowler, C.J.; Benedetti, M.S. The metabolism of dopamine by both forms of monoamine oxidase in the rat brain and its inhibition by cimoxatone. J. Neurochem., 1983, 40(6), 1534-1541.
[http://dx.doi.org/10.1111/j.1471-4159.1983.tb08123.x] [PMID: 6406646]
[41]
Madabhushi, R.; Pan, L.; Tsai, L-H. DNA damage and its links to neurodegeneration. Neuron, 2014, 83(2), 266-282.
[http://dx.doi.org/10.1016/j.neuron.2014.06.034] [PMID: 25033177]

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