Login Register Cart 0
Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

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

A Nanoinformatics Approach to Evaluate the Pharmacological Properties of Nanoparticles for the Treatment of Alzheimer’s Disease

Author(s): Muhammad Zohaib Nawaz, Syed Awais Attique , Qurat-ul-Ain, Fahdah Ayed Alshammari , Heba Waheeb Alhamdi , Huda Ahmed Alghamdi * and Wei Yan*

Volume 25, Issue 4, 2022

Published on: 17 February, 2021

Page: [730 - 737] Pages: 8

DOI: 10.2174/1386207324666210217145733

Price: $65

Abstract

Background: Alzheimer’s disease is a destructive nervous system disease which causes structural, biochemical and electrical abnormalities inside the human brain and results due to genetic and various environmental factors. Traditional therapeutic agents of Alzheimer’s disease such as tacrine and physostigmine have been found to cause adverse effects to the nervous system and gastrointestinal tract. Nanomaterials like graphene, metals, carbon-nanotubes and metal-oxides are gaining attention as potential drugs against Alzheimer’s disease due to their properties such as large surface area, which provide clinical efficiency, targeted drug designing and delivery.

Objectives: Designing new drugs by using experimental approaches is a time-consuming, tedious and laborious process which also requires advanced technologies. This study aims to identify some novel drug candidates against Alzheimer’s disease with no or less associated side effects using molecular docking approaches

Methods: In this study, we utilized nanoinformatics based approaches for evaluating the interaction properties of various nanomaterials and metal nanoparticles with the drug targets, including TRKB kinase domain, EphA4 and histone deacetylase. Furthermore, the drug-likeness of carbon nanotubes was confirmed through ADME analysis.

Results: Carbon nanotubes, either single or double-walled in all the three-configurations, including zigzag, chiral, and armchair forms, are found to interact with the target receptors with varying affinities

Conclusion: This study provides novel and clearer insights into the interaction properties and drug suitability of known putative nanoparticles as potential agents for the treatment of Alzheimer’s disease.

Keywords: Alzheimer’s disease, nanomaterials, molecular docking, drug likeness, pharmacological properties

« Previous Next »
Graphical Abstract

[1]
Bachurin, S.O.; Bovina, E.V.; Ustyugov, A.A. Drugs in clinical trials for Alzheimer’s disease: the major trends. Med. Res. Rev., 2017, 37(5), 1186-1225.
[http://dx.doi.org/10.1002/med.21434] [PMID: 28084618]
[2]
Bird, T.D. Genetic aspects of Alzheimer disease. Genet. Med., 2008, 10(4), 231-239.
[http://dx.doi.org/10.1097/GIM.0b013e31816b64dc] [PMID: 18414205]
[3]
Alzheimer’s. A. Alzheimer’s Association. 2015 Alzheimer’s disease facts and figures. Alzheimers Dement., 2015, 11(3), 332-384.
[http://dx.doi.org/10.1016/j.jalz.2015.02.003] [PMID: 25984581]
[4]
Berrios, G.E. Alzheimer’s disease: a conceptual history. Int. J. Geriatr. Psychiatry, 1990, 5(6), 355-365.
[http://dx.doi.org/10.1002/gps.930050603]
[5]
Skaper, S.D. Alzheimer’s disease and amyloid: culprit or coincidence? Int. Rev. Neurobiol., 2012, 102, 277-316.
[http://dx.doi.org/10.1016/B978-0-12-386986-9.00011-9] [PMID: 22748834]
[6]
Yoshida, S.; Suzuki, N. Antiamnesic and cholinomimetic side-effects of the cholinesterase inhibitors, physostigmine, tacrine and NIK-247 in rats. Eur. J. Pharmacol., 1993, 250(1), 117-124.
[http://dx.doi.org/10.1016/0014-2999(93)90628-U] [PMID: 8119309]
[7]
Casey, D.A.; Antimisiaris, D.; O’Brien, J. Drugs for Alzheimer’s disease: are they effective? P&T, 2010, 35(4), 208-211.
[PMID: 20498822]
[8]
Ridha, B.H.; Josephs, K.A.; Rossor, M.N. Delusions and hallucinations in dementia with Lewy bodies: worsening with memantine. Neurology, 2005, 65(3), 481-482.
[http://dx.doi.org/10.1212/01.wnl.0000172351.95783.8e] [PMID: 16087923]
[9]
Kumar, G.P.; Khanum, F. Neuroprotective potential of phytochemicals. Pharmacogn. Rev., 2012, 6(12), 81-90.
[http://dx.doi.org/10.4103/0973-7847.99898] [PMID: 23055633]
[10]
Howes, M.J.; Houghton, P.J. Ethnobotanical treatment strategies against Alzheimer’s disease. Curr. Alzheimer Res., 2012, 9(1), 67-85.
[http://dx.doi.org/10.2174/156720512799015046] [PMID: 22329652]
[11]
Marciani, D.J. Rejecting the Alzheimer’s disease vaccine development for the wrong reasons. Drug Discov. Today, 2017, 22(4), 609-614.
[http://dx.doi.org/10.1016/j.drudis.2016.10.012] [PMID: 27989721]
[12]
Xue, X.; Wang, L-R.; Sato, Y.; Jiang, Y.; Berg, M.; Yang, D-S.; Nixon, R.A.; Liang, X.J. Single-walled carbon nanotubes alleviate autophagic/lysosomal defects in primary glia from a mouse model of Alzheimer’s disease. Nano Lett., 2014, 14(9), 5110-5117.
[http://dx.doi.org/10.1021/nl501839q] [PMID: 25115676]
[13]
Yang, Z.; Ge, C.; Liu, J.; Chong, Y.; Gu, Z.; Jimenez-Cruz, C.A.; Chai, Z.; Zhou, R. Destruction of amyloid fibrils by graphene through penetration and extraction of peptides. Nanoscale, 2015, 7(44), 18725-18737.
[http://dx.doi.org/10.1039/C5NR01172H] [PMID: 26503908]
[14]
Merkle, R.C. Computational nanotechnology. Nanotechnology, 1991, 2(3), 134.
[http://dx.doi.org/10.1088/0957-4484/2/3/005]
[15]
Doke, S.K.; Dhawale, S.C. Alternatives to animal testing: A review. Saudi Pharm. J., 2015, 23(3), 223-229.
[http://dx.doi.org/10.1016/j.jsps.2013.11.002] [PMID: 26106269]
[16]
Krishnaraj, R.N.; Samanta, D.; Sani, R.K. Computational Nanotechnology: A Tool for Screening Therapeutic Nanomaterials Against Alzheimer’s Disease.Computational Modeling of Drugs Against Alzheimer’s Disease; Springer, 2018, pp. 613-635.
[http://dx.doi.org/10.1007/978-1-4939-7404-7_21]
[17]
Liu, Y.; Xu, L-P.; Dai, W.; Dong, H.; Wen, Y.; Zhang, X. Graphene quantum dots for the inhibition of & amyloid aggregation. Nanoscale, 2015, 7(45), 19060-19065.
[http://dx.doi.org/10.1039/C5NR06282A] [PMID: 26515666]
[18]
Chen, J.; Wang, J.; Yin, B.; Pang, L.; Wang, W. Zhu, WJAcn. Molecular mechanism of binding selectivity of inhibitors toward BACE1 and BACE2 revealed by multiple short molecular dynamics simulations and free-energy predictions. ACS Chemical Neuroscience, 2019, 10(10), 4303-4318.
[19]
Chen, J.; Liu, X.; Zhang, S.; Chen, J.; Sun, H.; Zhang, L. Molecular mechanism with regard to the binding selectivity of inhibitors toward FABP5 and FABP7 explored by multiple short molecular dynamics simulations and free energy analyses. Physical Chemistry Chemical Physics., 2020, 22(4), 2262-2275.
[http://dx.doi.org/10.1039/C9CP05704H]
[20]
Roy, U.; Luck, L.A. Molecular modeling of estrogen receptor using molecular operating environment. Biochem. Mol. Biol. Educ., 2007, 35(4), 238-243.
[http://dx.doi.org/10.1002/bmb.65] [PMID: 21591100]
[21]
Donaldson, K.; Murphy, F.A.; Duffin, R. Poland, CAJP toxicology f. Asbestos, carbon nanotubes and the pleural mesothelium: a review of the hypothesis regarding the role of long fibre retention in the parietal pleura, inflammation and mesothelioma. Particle and Fibre Toxicology, 2010, 7(1), 5.
[22]
Poland, C.A.; Duffin, R.; Kinloch, I.; Maynard, A.; Wallace, W.A.; Seaton, A. Carbon nanotubes introduced into the abdominal cavity of mice show asbestos-like pathogenicity in a pilot study. Nature Nanotechnology, 2008, 3(7), 5.
[http://dx.doi.org/10.1038/nnano.2008.111]
[23]
Zhang, M-Q.; Wilkinson, B. Drug discovery beyond the ‘rule-of-five’. Curr. Opin. Biotechnol., 2007, 18(6), 478-488.
[http://dx.doi.org/10.1016/j.copbio.2007.10.005] [PMID: 18035532]
[24]
Poppe, L; Rué, L; Timmers, M; Lenaerts, A; Storm, A; Callaerts-Vegh, Z EphA4 loss improves social memory performance and alters dendritic spine morphology without changes in amyloid pathology in a mouse model of Alzheimer’s disease., 2019, 11(1), 1-13.
[25]
Connor, B; Young, D; Lawlor, P; Gai, W; Waldvogel, H; Faull, R Trk receptor alterations in Alzheimer's disease., 1996, 42(1), 1-13.
[http://dx.doi.org/10.1016/S0169-328X(96)00040-X]
[26]
Cuadrado-Tejedor, M; Pérez González, M; García-Muñoz, C; Muruzabal, D; García-Barroso, C; Rabal, O. Taking advantage of the selectivity of histone deacetylases and phosphodiesterase inhibitors to design better therapeutic strategies to treat Alzheimer’s disease., 2019, 11, 149.
[http://dx.doi.org/10.3389/fnagi.2019.00149]
[27]
Hanwell, M.D.; Curtis, D.E.; Lonie, D.C.; Vandermeersch, T.; Zurek, E.; Hutchison, G.R. Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. J. Cheminform., 2012, 4(1), 17.
[http://dx.doi.org/10.1186/1758-2946-4-17] [PMID: 22889332]
[28]
Alavijeh, M.S.; Chishty, M.; Qaiser, M.Z.; Palmer, A.M. Drug metabolism and pharmacokinetics, the blood-brain barrier, and central nervous system drug discovery. NeuroRx, 2005, 2(4), 554-571.
[http://dx.doi.org/10.1602/neurorx.2.4.554] [PMID: 16489365]
[29]
Gu, S.; Fu, W.Y.; Fu, A.K.Y.; Tong, E.P.S.; Ip, F.C.F.; Huang, X.; Ip, N.Y. Identification of new EphA4 inhibitors by virtual screening of FDA-approved drugs. Sci. Rep., 2018, 8(1), 7377.
[http://dx.doi.org/10.1038/s41598-018-25790-1] [PMID: 29743517]
[30]
Drilon, A. TRK inhibitors in TRK fusion-positive cancers. Annals of Oncology., 2019, 30, viii23-viii30.
[http://dx.doi.org/10.1093/annonc/mdz282]
[31]
Eckschlager, T.; Plch, J.; Stiborova, M.; Hrabeta, J. Histone Deacetylase Inhibitors as Anticancer Drugs. Int. J. Mol. Sci., 2017, 18(7), E1414.
[http://dx.doi.org/10.3390/ijms18071414] [PMID: 28671573]
[32]
Sajjad, R.; Arif, R.; Shah, A.; Manzoor, I.; Mustafa, G. Pathogenesis of Alzheimer’s Disease: Role of Amyloid-beta and Hyperphosphorylated Tau Protein. Indian J. Pharm. Sci., 2018, 80(4), 581-591.
[http://dx.doi.org/10.4172/pharmaceutical-sciences.1000397]
[33]
Zhuang, Z-P.; Kung, M-P.; Hou, C.; Skovronsky, D.M.; Gur, T.L.; Plössl, K.; Trojanowski, J.Q.; Lee, V.M.; Kung, H.F. Radioiodinated styrylbenzenes and thioflavins as probes for amyloid aggregates. J. Med. Chem., 2001, 44(12), 1905-1914.
[http://dx.doi.org/10.1021/jm010045q] [PMID: 11384236]
[34]
Smith, Q.R. A review of blood-brain barrier transport techniques.The Blood-Brain Barrier; Springer, 2003, pp. 193-208.
[35]
Huang, X.; Cuajungco, M.P.; Atwood, C.S.; Hartshorn, M.A.; Tyndall, J.D.; Hanson, G.R.; Stokes, K.C.; Leopold, M.; Multhaup, G.; Goldstein, L.E.; Scarpa, R.C.; Saunders, A.J.; Lim, J.; Moir, R.D.; Glabe, C.; Bowden, E.F.; Masters, C.L.; Fairlie, D.P.; Tanzi, R.E.; Bush, A.I. Cu(II) potentiation of alzheimer abeta neurotoxicity. Correlation with cell-free hydrogen peroxide production and metal reduction. J. Biol. Chem., 1999, 274(52), 37111-37116.
[http://dx.doi.org/10.1074/jbc.274.52.37111] [PMID: 10601271]
[36]
Ritchie, C.W.; Bush, A.I.; Mackinnon, A.; Macfarlane, S.; Mastwyk, M.; MacGregor, L.; Kiers, L.; Cherny, R.; Li, Q.X.; Tammer, A.; Carrington, D.; Mavros, C.; Volitakis, I.; Xilinas, M.; Ames, D.; Davis, S.; Beyreuther, K.; Tanzi, R.E.; Masters, C.L. Metal-protein attenuation with iodochlorhydroxyquin (clioquinol) targeting Abeta amyloid deposition and toxicity in Alzheimer disease: a pilot phase 2 clinical trial. Arch. Neurol., 2003, 60(12), 1685-1691.
[http://dx.doi.org/10.1001/archneur.60.12.1685] [PMID: 14676042]
[37]
Roney, C.; Kulkarni, P.; Arora, V.; Antich, P.; Bonte, F.; Wu, A.; Mallikarjuana, N.N.; Manohar, S.; Liang, H.F.; Kulkarni, A.R.; Sung, H.W.; Sairam, M.; Aminabhavi, T.M. Targeted nanoparticles for drug delivery through the blood-brain barrier for Alzheimer’s disease. J. Control. Release, 2005, 108(2-3), 193-214.
[http://dx.doi.org/10.1016/j.jconrel.2005.07.024] [PMID: 16246446]
[38]
Jain, S.K.; Gupta, Y.; Jain, A.; Saxena, A.R.; Khare, P.; Jain, A. Mannosylated gelatin nanoparticles bearing an anti-HIV drug didanosine for site-specific delivery. Nanomedicine (Lond.), 2008, 4(1), 41-48.
[http://dx.doi.org/10.1016/j.nano.2007.11.004] [PMID: 18207463]
[39]
Wilson, B.; Samanta, M.K.; Santhi, K.; Kumar, K.P.; Ramasamy, M.; Suresh, B. Chitosan nanoparticles as a new delivery system for the anti-Alzheimer drug tacrine. Nanomedicine (Lond.), 2010, 6(1), 144-152.
[http://dx.doi.org/10.1016/j.nano.2009.04.001] [PMID: 19446656]

Rights & Permissions Print Cite
Article Metrics
39
1
© 2024 Bentham Science Publishers | Privacy Policy