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Current Topics in Medicinal Chemistry

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ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

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Review Article

In silico Strategy: A Promising Implement in the Development of Multitarget Drugs against Neurodegenerative Diseases

Author(s): Purusottam Banjare, Balaji Wamanrao Matore, Anjali Murmu, Vikash Kumar, Jagadish Singh and Partha Pratim Roy*

Volume 23, Issue 29, 2023

Published on: 31 August, 2023

Page: [2765 - 2791] Pages: 27

DOI: 10.2174/1568026623666230811113231

Price: $65

Abstract

Multi-target drug development (MTDD) is the demand of the recent era, especially in the case of multi-factorial conditions such as cancer, depression, neurodegenerative diseases (NDs), etc. The MTDD approaches have many advantages; avoidance of drug-drug interactions, predictable pharmacokinetic profile, and less drug resistance. The wet lab practice in MTDD is very challenging for the researchers, and the chances of late-stage failure are obvious. Identification of an appropriate target (Target fishing) is another challenging task in the development of multi-target drugs. The in silico tools will be one of the promising tools in the MTDD for the NDs. Therefore the outlook of the review comprises a short description of NDs, target associated with different NDs, in silico studies so far done for MTDD for various NDs. The main thrust of this review is to explore the present and future aspects of in silico tools used in MTDD for different NDs in combating the challenge of drug development and the application of various in silico tools to solve the problem of target fishing.

Keywords: ND, MTDD, Drug resistance, Target fishing, Docking, In silico, QSAR.

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[1]
Ramsay, R.R.; Popovic-Nikolic, M.R.; Nikolic, K.; Uliassi, E.; Bolognesi, M.L. A Perspective on Multi-target Drug Discovery and Design for Complex Diseases. Clin. Transl. Med., 2018, 7.
[2]
Saginc, G.; Voellmy, F.; Linding, R. Cancer Systems Biology: Harnessing off-Target Effects. Nat. Chem. Biol., 2017, 13, 1204-1205.
[3]
Klaeger, S.; Heinzlmeir, S.; Wilhelm, M.; Polzer, H.; Vick, B.; Koenig, P.-A.; Reinecke, M.; Ruprecht, B.; Petzoldt, S.; Meng, C.; Zecha, J.; Reiter, K.; Qiao, H.; Helm, D.; Koch, H.; Schoof, M.; Canevari, G.; Casale, E.; Depaolini, S.R.; Feuchtinger, A.; Wu, Z.; Schmidt, T.; Rueckert, L.; Becker, W.; Huenges, J.; Garz, A.-K.; Gohlke, B.-O.; Zolg, D.P.; Kayser, G.; Vooder, T.; Preissner, R.; Hahne, H.; Tõnisson, N.; Kramer, K.; Götze, K.; Bassermann, F.; Schlegl, J.; Ehrlich, H.-C.; Aiche, S.; Walch, A.; Greif, P.A.; Schneider, S.; Felder, E.R.; Ruland, J.; Médard, G.; Jeremias, I.; Spiekermann, K.; Kuster, B. 2017.
[4]
Hopkins, A.L. Network Pharmacology: The next Paradigm in Drug Discovery. Nat. Chem. Biol., 2008, 4, 682-690.
[5]
Pilpel, Y.; Sudarsanam, P.; Church, G.M. Identifying Regulatory Networks by Combinatorial Analysis of Promoter Elements. Nat. Genet., 2001, 29, 153-159.
[6]
Overall, C.M.; Kleifeld, O. Validating Matrix Metalloproteinases as Drug Targets and Anti-Targets for Cancer Therapy. Nat. Rev. Cancer, 2006, 6, 227-239.
[7]
Force, T.; Krause, D.S.; Van Etten, R.A. Molecular Mechanisms of Cardiotoxicity of Tyrosine Kinase Inhibition. Nat. Rev. Cancer, 2007, 7, 332-344.
[8]
Paolini, G.V.; Shapland, R.H.B.; Van Hoorn, W.P.; Mason, J.S.; Hopkins, A.L. Global Mapping of Pharmacological Space. Nat. Biotechnol., 2006, 24, 805-815.
[9]
Zhang, W.; Bai, Y.; Wang, Y. 1, W.X. Polypharmacology in Drug Discovery: A Review from Systems Pharmacology Perspective. Curr. Pharm. Des., 2016, 22, 3171-3181.
[10]
Lauria, A.; Bonsignore, R.; Bartolotta, R.; Perricone, U. A.M. and C.G. Drugs Polypharmacology by in silico Methods: New Opportunities in Drug Discovery. Curr. Pharm. Des., 2016, 22, 3073.
[11]
Zhang, A.S.R.; Polypharmacology, S. Drug Discovery for the Future. Expert Rev. Clin. Pharmacol., 2013, 6.
[12]
Chaudhari, R.; Fong, L.W.; Tan, Z.; Huang, B.; Zhang, S. An Up-to-Date Overview of Computational Polypharmacology in Modern Drug Discovery. Expert Opin. Drug Discov., 2020, 15, 1025-1044.
[13]
Li, Y.Y.; Jones, S.J.; Smith, M. The Importance of Drug Repositioning in the Era of Genomic Medicine Drug Repositioning for Personalized Medicine R E V I E W. Genome Med., 2012, 4, 27.
[14]
Singh, T.U.; Parida, S.; Lingaraju, M.C.; Kesavan, M.; Kumar, D.; Singh, R.K. Drug Repurposing Approach to Fight COVID-19. Pharmacol. Rep., 2020, 72, 1479-1508.
[15]
https://news.un.org/en/story/2007/02/210312-nearly-1-6-worlds-population-suffer-neurological-disorders-un-report
[16]
Prince, M.; Knapp, M.G.; M, McCrone, P.; Prina, M.; Comas-Herrera, A.; Wittenberg, R.; Adelaja, B.; Hu, B.; King, D.; Rehill, A and Salimkumar, D. Dementia UK: Update; 2nd ed.; Alzheimer’s Society, 2018; Vol. 1.
[17]
World Health Organization, W. Dementia. https://www.who.int/news-room/fact-sheets/detail/dementia (Accessed Jun 27, 2022).
[18]
Baig, M.H.; Ahmad, K.; Rabbani, G.; Danishuddin, M.; Choi, I. Computer Aided Drug Design and Its Application to the Development of Potential Drugs for Neurodegenerative Disorders. Curr. Neuropharmacol., 2017, 16, 740-748.
[19]
Banjare, P.; Sarthi, A.S.; Singh, J. P.P. in silico Approaches in Drug Discovery and Design of Anti Allergic Agents. Frontiers in Clinical Drug Research-Anti-Allergy Agents, 2020, 4, 94-132.
[20]
Kannan, V.; Sitty, M.B.; Periyannan, M. Design Synthesis in silicoin vitro and in vivo Evaluation of Novel L-Cysteine Derivatives as Multi-Target-Directed Ligands for the Treatment of Neurodegenerative Diseases. Beni. Suef Univ. J. Basic Appl. Sci., 2018, 7, 452-460.
[21]
Gerovska, D.; Irizar, H.; Otaegi, D.; Ferrer, I.; López de Munain, A.; Araúzo-Bravo, M.J. Genealogy of the Neurodegenerative Diseases Based on a Meta-Analysis of Age-Stratified Incidence Data. Sci. Rep., 2020, 10, 1-15.
[22]
Speck-Planche, A.; Kleandrova, V. V. QSAR and Molecular Docking Techniques for the Discovery of Potent Monoamine Oxidase B Inhibitors: Computer-Aided Generation of New Rasagiline Bioisosteres. Curr. Top. Med. Chem., 2012, 12, 1734-1747.
[23]
Bishara, D.; Sauer, J.; Taylor, D. The Pharmacological Management of Alzheimer ’s Disease. Prog. Neurol. Psychiatry, 2015, 9-16.
[24]
Chaudhary, A.; Maurya, P.K.; Yadav, B.S.; Singh, S.; Mani, A. Current Therapeutic Targets for Alzheimer’s Disease. J. Biomed. (Syd.), 2018, 3, 74-84.
[25]
Singh, N.; Upadhyay, S.; Jaiswar, A.; Mishra, N. in silico Docking Studies and Potential Lead Identification against JNK3 for Alzheimer’s Disease. Int. J. Pharm. Investig., 2019, 9, 220-222.
[26]
Li, T.; Zhu, J. Entanglement of CCR5 and Alzheimer’s Disease. Front. Aging Neurosci., 2019, 10, 1-12.
[27]
Blaikie, L.; Kay, G.; Kong Thoo Lin, P. Current and Emerging Therapeutic Targets of Alzheimer’s Disease for the Design of Multi-Target Directed Ligands. MedChemComm, 2019, 10, 2052-2072.
[28]
Choudhary, D.K.; Kumar, M.; Prasad, R.; Kumar, V. In silico approach for sustainable agriculture. In: In silico approach for sustainable agriculture. , 2018; pp. 1-293.
[29]
García-Osta, A.; Cuadrado-Tejedor, M.; García-Barroso, C.; Oyarzábal, J.; Franco, R. Phosphodiesterases as Therapeutic Targets for Alzheimer’s Disease. ACS Chem. Neurosci., 2012, 3, 832-844.
[30]
Hoozemans, J.; Rozemuller, J.; van Haastert, E.; Veerhuis, R.; Eikelenboom, P. Cyclooxygenase-1 and -2 in the Different Stages of Alzheimers Disease Pathology. Curr. Pharm. Des., 2008, 14, 1419-1427.
[31]
Gazova, Z.; Soukup, O.; Sepsova, V.; Siposova, K.; Drtinova, L.; Jost, P.; Spilovska, K.; Korabecny, J.; Nepovimova, E.; Fedunova, D.; Horak, M.; Kaniakova, M.; Wang, Z.J.; Hamouda, A.K.; Kuca, K. Multi-Target-Directed Therapeutic Potential of 7-Methoxytacrine-Adamantylamine Heterodimers in the Alzheimer’s Disease Treatment. Biochim. Biophys. Acta Mol. Basis Dis., 2017, 1863, 607-619.
[32]
Wang, R.; Reddy, P.H. Role of Glutamate and NMDA Receptors in Alzheimer’s Disease. J. Alzheimers Dis., 2017, 57, 1041-1048.
[33]
Vieira, M.N.N.; Lyra e Silva, N.M.; Ferreira, S.T.; De Felice, F.G. Protein Tyrosine Phosphatase 1B (PTP1B): A Potential Target for Alzheimer’s Therapy? Front. Aging Neurosci., 2017, 9, 1-9.
[34]
Ferrero, H.; Solas, M.; Francis, P.T.; Ramirez, M.J. Serotonin 5-HT6 Receptor Antagonists in Alzheimer’s Disease: Therapeutic Rationale and Current Development Status. CNS Drugs, 2017, 31, 19-32.
[35]
Yarza, R.; Vela, S.; Solas, M.; Ramirez, M.J. C-Jun N-Terminal Kinase (JNK) Signaling as a Therapeutic Target for Alzheimer’s Disease. Front. Pharmacol., 2016, 6, 1-12.
[36]
Hamilton, A.; Esseltine, J.L.; Devries, R.A.; Cregan, S.P.; Ferguson, S.S.G. Metabotropic Glutamate Receptor 5 Knockout Reduces Cognitive Impairment and Pathogenesis in a Mouse Model of Alzheimer’s Disease. Mol. Brain, 2014, 7, 1-12.
[37]
Louzada, P.R.; Lima, A.C.P.; Mendonca-Silva, D.L.; Noël, F.; De Mello, F.G.; Ferreira, S.T. Taurine Prevents the Neurotoxicity of B-amyloid and Glutamate Receptor Agonists: Activation of GABA Receptors and Possible Implications for Alzheimer’s Disease and Other Neurological Disorders. FASEB J., 2004, 18, 511-518.
[38]
Kemppainen, N.; Laine, M.; Laakso, M.P.; Kaasinen, V.; Någren, K.; Vahlberg, T.; Kurki, T.; Rinne, J.O. Hippocampal Dopamine D2 Receptors Correlate with Memory Functions in Alzheimer’s Disease. Eur. J. Neurosci., 2003, 18, 149-154.
[39]
Savaskan, E.; Hock, C.; Olivieri, G.; Bruttel, S.; Rosenberg, C.; Hulette, C.; Müller-Spahn, F. Cortical Alterations of Angiotensin Converting Enzyme, Angiotensin II and AT1 Receptor in Alzheimer’s Dementia. Neurobiol. Aging, 2001, 22, 541-546.
[40]
Buxbaum, J.D.; Liu, K.N.; Luo, Y.; Slack, J.L.; Stocking, K.L.; Peschon, J.J.; Johnson, R.S.; Castner, B.J.; Cerretti, D.P.; Black, R.A. Evidence That Tumor Necrosis Factor α Converting Enzyme Is Involved in Regulated α-Secretase Cleavage of the Alzheimer Amyloid Protein Precursor. J. Biol. Chem., 1998, 273, 27765-27767.
[41]
Yoshimoto, M.; Iwai, A.; Kang, D.; Otero, D.A.C.; Xia, Y.; Saitoh, T. NACP, the Precursor Protein of the Non-Amyloid β/A4 Protein (Aβ) Component of Alzheimer Disease Amyloid, Binds Aβ and Stimulates Aβ Aggregation. Proc. Natl. Acad. Sci. USA, 1995, 92, 9141-9145.
[42]
Arndt, J.W.; Qian, F.; Smith, B.A.; Quan, C.; Kilambi, K.P.; Bush, M.W.; Walz, T.; Pepinsky, R.B.; Bussière, T.; Hamann, S.; Cameron, T.O.; Weinreb, P.H. Structural and Kinetic Basis for the Selectivity of Aducanumab for Aggregated Forms of Amyloid-β. Sci. Rep., 2018, 8, 6412.
[43]
Wu, A.T.H.; Lawal, B.; Wei, L.; Wen, Y-T.; Tzeng, D.T.W.; Lo, W-C. Multiomics Identification of Potential Targets for Alzheimer Disease and Antrocin as a Therapeutic Candidate. Pharmaceutics, 2021, 13, 1555.
[44]
Carradori, S.; Ortuso, F.; Petzer, A.; Bagetta, D.; De Monte, C.; Secci, D.; De Vita, D.; Guglielmi, P.; Zengin, G.; Aktumsek, A.; Alcaro, S.; Petzer, J.P. Design, Synthesis and Biochemical Evaluation of Novel Multi-Target Inhibitors as Potential Anti-Parkinson Agents. Eur. J. Med. Chem., 2018, 143, 1543-1552.
[45]
Ionescu, M.I. Molecular Docking Investigation of the Amantadine Binding to the Enzymes Upregulated or Downregulated in Parkinson’s Disease. ADMET DMPK, 2020, 8, 149-175.
[46]
Title, N. https://parkinsonsnewstoday.com/parkinsons-disease-statistics
[47]
Title, No. https://www.parkinson.org/pd-library/newsletters/parkinson-report-spring-2015
[48]
Cheong, S.L.; Federico, S.; Spalluto, G.; Klotz, K.N.; Pastorin, G. The Current Status of Pharmacotherapy for the Treatment of Parkinson’s Disease: Transition from Single-Target to Multitarget Therapy. Drug Discov. Today, 2019, 24, 1769-1783.
[49]
Huang, Y.; Chan, P.; Halliday, G. Genetics of Parkinson’s Disease; , 2007, pp. 663-697.
[50]
Trang, A.; Physiology, K.P. Acetylcholinesterase; , 2020. [Internet
[51]
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, 57100994
[52]
Załuski, M.; Schabikowski, J.; Schlenk, M.; Olejarz-Maciej, A.; Kubas, B.; Karcz, T.; Kuder, K.; Latacz, G.; Zygmunt, M.; Synak, D.; Hinz, S.; Müller, C.E.; Kieć-Kononowicz, K. Novel Multi-Target Directed Ligands Based on Annelated Xanthine Scaffold with Aromatic Substituents Acting on Adenosine Receptor and Monoamine Oxidase B. Synthesis, in vitro and in silico Studies. Bioorg. Med. Chem., 2019, 27, 1195-1210.
[53]
Wilson, H.; Pagano, G.; Niccolini, F.; Muhlert, N.; Mehta, M.A.; Searle, G.; Gunn, R.N.; Rabiner, E.A.; Foltynie, T.; Politis, M. The Role of Phosphodiesterase 4 in Excessive Daytime Sleepiness in Parkinson’s Disease. Parkinsonism Relat. Disord., 2020, 77, 163-169.
[54]
Zhang, J.; Li, X.; Da Li, J. The Roles of Post-Translational Modifications on α-Synuclein in the Pathogenesis of Parkinson’s Diseases. Front. Neurosci., 2019, 13.
[55]
Lu, R.; Zhao, X.; Li, J.; Niu, P.; Yang, B.; Wu, H.; Wang, W.; Song, H.; Huang, B.; Zhu, N.; Bi, Y.; Ma, X.; Zhan, F.; Wang, L.; Hu, T.; Zhou, H.; Hu, Z.; Zhou, W.; Zhao, L.; Chen, J.; Meng, Y.; Wang, J.; Lin, Y.; Yuan, J.; Xie, Z.; Ma, J.; Liu, W.J.; Wang, D.; Xu, W.; Holmes, E.C.; Gao, G.F.; Wu, G.; Chen, W.; Shi, W.; Tan, W. Articles Genomic Characterisation and Epidemiology of 2019 Novel Coronavirus : Implications for Virus Origins and Receptor Binding. Lancet, 2020, 395, 565-574.
[56]
Rui, Q.; Ni, H.; Li, D.; Gao, R.; Chen, G. The Role of LRRK2 in Neurodegeneration of Parkinson Disease. Curr. Neuropharmacol., 2018, 16, 1348-1357.
[57]
Hansen, K.B.; Yi, F.; Perszyk, R.E.; Furukawa, H.; Wollmuth, L.P.; Gibb, A.J.; Traynelis, S.F. Structure, Function, and Allosteric Modulation of NMDA Receptors. J. Gen. Physiol., 2018, 150, 1081-1105.
[58]
Belarbi, K.; Cuvelier, E.; Destée, A.; Gressier, B.; Chartier-Harlin, M.C. NADPH Oxidases in Parkinson’s Disease: A Systematic Review. Mol. Neurodegener., 2017, 12, 1-18.
[59]
Plaitakis, A.; Kalef-Ezra, E.; Kotzamani, D.; Zaganas, I.; Spanaki, C. The Glutamate Dehydrogenase Pathway and Its Roles in Cell and Tissue Biology in Health and Disease. Biology (Basel), 2017, 6, 1-26.
[60]
Azam, F.; Mohamed, N.; Alhussen, F. Molecular Interaction Studies of Green Tea Catechins as Multitarget Drug Candidates for the Treatment of Parkinsons Disease: Computational and Structural Insights. Netw. Comput. Neural Syst., 2015, 26, 97-115.
[61]
Sheth, S.; Brito, R.; Mukherjea, D.; Rybak, L.P.; Ramkumar, V. Adenosine Receptors: Expression, Function and Regulation. Int. J. Mol. Sci., 2014, 15, 2024-2052.
[62]
Gasparini, F.; Di Paolo, T.; Gomez-Mancilla, B. Metabotropic Glutamate Receptors for Parkinson’s Disease Therapy., 2013.
[63]
Youdim, M.B.H.; Bakhle, Y.S. Monoamine Oxidase: Isoforms and Inhibitors in Parkinson’s Disease and Depressive Illness. Br. J. Pharmacol., 2006, 147.
[64]
Salgin-Gökşen, U.; Yabanoǧlu-Çiftçi, S.; Ercan, A.; Yelekçi, K.; Uçar, G.; Gökhan-Kelekçi, N. Evaluation of Selective Human MAO Inhibitory Activities of Some Novel Pyrazoline Derivatives. J. Neural Transm. (Vienna), 2013, 120, 863-873.
[65]
Lei, P.; Ayton, S.; Bush, A.I.; Adlard, P.A. GSK-3 in Neurodegenerative Diseases. Int. J. Alzheimers. Dis., 2011, 2011.
[66]
Carta, A.R.; Pisanu, A.; Carboni, E. Do PPAR-Gamma Agonists Have a Future in Parkinson’s Disease Therapy?, 2011.
[67]
Buckholtz, J.W.; Meyer-Lindenberg, A. MAOA and the Neurogenetic Architecture of Human Aggression. Trends Neurosci., 2008, 31, 120-129.
[68]
Aquilano, K.; Baldelli, S.; Rotilio, G.; Ciriolo, M.R. Role of Nitric Oxide Synthases in Parkinson’s Disease: A Review on the Antioxidant and Anti-Inflammatory Activity of Polyphenols. Neurochem. Res., 2008, 33, 2416-2426.
[69]
Sibley, R. A links open overlay panelKimNeveDavid. D4 Dopamine Receptor. xPharm Compr. Pharmacol. Ref., 2007, 1-12.
[70]
Bilder, R.M.; Volavka, J.; Lachman, H.M.; Grace, A.A. The Catechol-O-Methyltransferase Polymorphism: Relations to the Tonic-Phasic Dopamine Hypothesis and Neuropsychiatric Phenotypes. Neuropsychopharmacology, 2004, 29, 1943-1961.
[71]
Peng, J.; Andersen, J.K. The Role of C-Jun N-Terminal Kinase (JNK) in Parkinson’s Disease. IUBMB Life, 2003, 55, 267-271.
[72]
Murray, T.K.; Whalley, K.; Robinson, C.S.; Ward, M.A.; Hicks, C.A.; Lodge, D.; Vandergriff, J.L.; Baumbarger, P.; Siuda, E.; Gates, M.; Ogden, A.M.; Skolnick, P.; Zimmerman, D.M.; Nisenbaum, E.S.; Bleakman, D.; O’Neill, M.J. LY503430, a Novel α-Amino-3-Hydroxy-5-Methylisoxazole-4-Propionic Acid Receptor Potentiator with Functional, Neuroprotective and Neurotrophic Effects in Rodent Models of Parkinson’s Disease. J. Pharmacol. Exp. Ther., 2003, 306, 752-762.
[73]
Lücking, C.B.; Brice, A. Alpha-Synuclein and Parkinson’s Disease. Cell. Mol. Life Sci., 2000, 57, 1894-1908.
[74]
Imming, P.; Sinning, C.; Meyer, A. Drugs, Their Targets and the Nature and Number of Drug Targets. Nat. Rev. Drug Discov., 2006, 5, 821-834.
[75]
Berlin, I.; de Brettes, B.; Aymard, G.; Diquet, B.; Arnulf, I.; Puech, A.J. Dopaminergic Drug Response and the Genotype (Taq IA Polymorphism) of the Dopamine D2 Receptor. Int. J. Neuropsychopharmacol., 2000, 3S1461145700001711
[76]
Friedman, J.H. Pimavanserin for the Treatment of Parkinson’s Disease Psychosis. Expert Opin. Pharmacother., 2013, 14, 1969-1975.
[77]
Tabrizi, S.J.; Flower, M.D.; Ross, C.A.; Wild, E.J. Huntington Disease: New Insights into Molecular Pathogenesis and Therapeutic Opportunities. Nat. Rev. Neurol., 2020, 16, 529-546.
[78]
Jimenez-Sanchez, M.; Licitra, F.; Underwood, B.R.; Rubinsztein, D.C. Huntington’s Disease: Mechanisms of Pathogenesis and Therapeutic Strategies. Cold Spring Harb. Perspect. Med., 2017, 7, 1-22.
[79]
Gil, J.M.; Rego, A.C. Mechanisms of Neurodegeneration in Huntington’s Disease. Eur. J. Neurosci., 2008, 27, 2803-2820.
[80]
Disorders, N.O. https://rarediseases.org/rare-diseases/huntingtons-disease/#affected-populations
[81]
Ghosh, R.; Tabrizi, S.J. Clinical features of Huntington’s Disease. In: 2018.
[82]
Ross, C.A.; Tabrizi, S. J. Huntington’s Disease: From Molecular Pathogenesis to Clinical Treatment. Lancet Neurol., 2011, 10, 83-98.
[83]
Bashir, H. Emerging Therapies in Huntington’s Disease. Expert Rev. Neurother., 2019, 19, 983-995.
[84]
Choi, S.H.; Cho, K.J. LAMP2A-Mediated Autophagy Involved in Huntington’s Disease Progression. Biochem. Biophys. Res. Commun., 2021, 534, 561-567.
[85]
Angelopoulou, E.; Paudel, Y.N.; Piperi, C. Exploring the Role of High-Mobility Group Box 1 (HMGB1) Protein in the Pathogenesis of Huntington’s Disease. J. Mol. Med. (Berl.), 2020, 98, 325-334.
[86]
Yusuf, I.O.; Chen, H.M.; Cheng, P.H.; Chang, C. Y.; Tsai, S.J.; Chuang, J.I.; Wu, C.C.; Huang, B.M.; Sun, H.S.; Chen, C.M.; Yang, S.H. 2020.
[87]
Voisin, J.; Farina, F.; Naphade, S.; Fontaine, M.; Tshilenge, K.T.; Galicia Aguirre, C.; Lopez-Ramirez, A.; Dancourt, J.; Ginisty, A.; Sasidharan Nair, S.; Lakshika Madushani, K.; Zhang, N.; Lejeune, F.X.; Verny, M.; Campisi, J.; Ellerby, L.M.; Neri, C. FOXO3 Targets Are Reprogrammed as Huntington’s Disease Neural Cells and Striatal Neurons Face Senescence with P16INK4a Increase. Aging Cell, 2020, 19, 1-15.
[88]
Moreno-Delgado, D.; Puigdellívol, M.; Moreno, E.; Rodríguez-Ruiz, M.; Botta, J.; Gasperini, P.; Chiarlone, A.; Howell, L.A.; Scarselli, M.; Casadó, V.; Cortés, A.; Ferré, S.; Guzmán, M.; Lluís, C.; Alberch, J.; Canela, E.I.; Ginés, S.; McCormick, P.J. Modulation of Dopamine D1 Receptors via Histamine H3 Receptors Is a Novel Therapeutic Target for Huntington’s Disease. eLife, 2020, 9, 1-31.
[89]
Hegde, R.N.; Chiki, A.; Petricca, L.; Martufi, P.; Arbez, N.; Mouchiroud, L.; Auwerx, J.; Landles, C.; Bates, G.P.; Singh-Bains, M.K.; Dragunow, M.; Curtis, M.A.; Faull, R.L.; Ross, C.A.; Caricasole, A.; Lashuel, H.A. TBK1 Phosphorylates Mutant Huntingtin and Suppresses Its Aggregation and Toxicity in Huntington’s Disease Models. EMBO J., 2020, 39, 1-25.
[90]
Khan, H.; Tundis, R.; Ullah, H.; Aschner, M.; Belwal, T.; Mirzaei, H. E.K.A. Flavonoids Targeting NRF2 in Neurodegenerative Disorders. Food Chem. Toxicol., 2020, 146111817
[91]
García-Huerta, P.; Troncoso-Escudero, P.; Wu, D.; Thiruvalluvan, A.; Cisternas-Olmedo, M.; Henríquez, D.R.; Plate, L.; Chana-Cuevas, P.; Saquel, C.; Thielen, P.; Longo, K.A.; Geddes, B.J.; Lederkremer, G.Z.; Sharma, N.; Shenkman, M.; Naphade, S.; Sardi, S.P.; Spichiger, C.; Richter, H.G.; Court, F.A.; Tshilenge, K.T.; Ellerby, L.M.; Wiseman, R.L.; Gonzalez-Billault, C.; Bergink, S.; Vidal, R.L.; Hetz, C. Insulin-like Growth Factor 2 (IGF2) Protects against Huntington’s Disease through the Extracellular Disposal of Protein Aggregates. Acta Neuropathol., 2020, 140, 737-764.
[92]
Andrews, K.; Josiah, S.S.; Zhang, J. The Therapeutic Potential of Neuronal K-Cl Co- Transporter KCC2 in Huntington’s Disease and Its Comorbidities. Int. J. Mol. Sci., 2020, 21, 1-21.
[93]
Sharma, M.; Rajendrarao, S.; Shahani, N.; Ramírez-Jarquín, U.N.; Subramaniam, S. Cyclic GMP-AMP Synthase Promotes the Inflammatory and Autophagy Responses in Huntington Disease. Proc. Natl. Acad. Sci. USA, 2020, 117, 15989-15999.
[94]
Yin, P.; Liu, Q.; Pan, Y.; Yang, W.; Yang, S.; Wei, W.; Chen, X.; Hong, Y.; Bai, D.; Li, X.; Li, S. Phosphorylation of Myelin Regulatory Factor by PRKG 2 Mediates Demyelination in Huntington’s Disease. EMBO Rep., 2020, 21.
[95]
De Souza, J.M.; Abd-elrahman, K.S.; Ribeiro, F.M.; Ferguson, S.S.G. MGluR5 Regulates REST/NRSF Signaling through N-Cadherin/β-Catenin Complex in Huntington’s Disease. Mol. Brain, 2020, 13, 1-15.
[96]
Ganz, J.; Shacham, T.; Kramer, M.; Shenkman, M.; Eiger, H.; Weinberg, N.; Iancovici, O.; Roy, S.; Simhaev, L.; Da’adoosh, B.; Engel, H.; Perets, N.; Barhum, Y.; Portnoy, M.; Offen, D.; Lederkremer, G.Z. A Novel Specific PERK Activator Reduces Toxicity and Extends Survival in Huntington’s Disease Models. Sci. Rep., 2020, 10, 1-15.
[97]
Federspiel, J.D.; Greco, T.M.; Lum, K.K.; Cristea, I.M. Hdac4 Interactions in Huntington’s Disease Viewed through the Prism of Multiomics. Mol. Cell. Proteomics, 2019, 18, S92-S113.
[98]
Yildirim, F.; Ng, C.W.; Kappes, V.; Ehrenberger, T.; Rigby, S.K.; Stivanello, V.; Gipson, T.A.; Soltis, A.R.; Vanhoutte, P.; Caboche, J.; Housman, D.E.; Fraenkel, E. Early Epigenomic and Transcriptional Changes Reveal Elk-1 Transcription Factor as a Therapeutic Target in Huntington’s Disease. Proc. Natl. Acad. Sci. USA, 2019, 116, 24840-24851.
[99]
Boros, F.A.; Klivényi, P.; Toldi, J.; Vécsei, L. Indoleamine 2,3-Dioxygenase as a Novel Therapeutic Target for Huntington’s Disease. Expert Opin. Ther. Targets, 2019, 23, 39-51.
[100]
Lois, C.; González, I.; Izquierdo-García, D.; Zürcher, N.R.; Wilkens, P.; Loggia, M.L.; Hooker, J.M.; Rosas, H.D. Neuroinflammation in Huntington’s Disease: New Insights with 11C-PBR28 PET/MRI. ACS Chem. Neurosci., 2018, 9, 2563-2571.
[101]
Song, H.; Li, H.; Guo, S.; Pan, Y.; Fu, Y.; Zhou, Z.; Li, Z.; Wen, X.; Sun, X.; He, B.; Gu, H.; Zhao, Q.; Wang, C.; An, P.; Luo, S.; Hu, Y.; Xie, X.; Lu, B. Targeting Gpr52 Lowers Mutant HTT Levels and Rescues Huntington’s Disease-Associated Phenotypes. Brain, 2018, 141, 1782-1798.
[102]
Di Pardo, A.; Maglione, V. The S1P Axis: New Exciting Route for Treating Huntington’s Disease. Trends Pharmacol. Sci., 2018, 39, 468-480.
[103]
Krzyzosiak, A.; Sigurdardottir, A.; Luh, L.; Carrara, M.; Das, I.; Schneider, K.; Bertolotti, A. Target-Based Discovery of an Inhibitor of the Regulatory Phosphatase PPP1R15B. Cell, 2018, 174, 1216-1228.e19.
[104]
Moruno-Manchon, J.F.; Uzor, N.E.; Blasco-Conesa, M.P.; Mannuru, S.; Putluri, N.; Furr-Stimming, E.E.; Tsvetkov, A.S. Inhibiting Sphingosine Kinase 2 Mitigates Mutant Huntingtin-Induced Neurodegeneration in Neuron Models of Huntington Disease. Hum. Mol. Genet., 2017, 26, 1305-1317.
[105]
Coppen, E.M.; Roos, R.A.C. Current Pharmacological Approaches to Reduce Chorea in Huntington’s Disease. Drugs, 2017, 77, 29-46.
[106]
Marelli, C.; Maschat, F. The P42 Peptide and Peptide-Based Therapies for Huntington’s Disease. Orphanet J. Rare Dis., 2016, 11.
[107]
Amin, S.A.; Adhikari, N.; Jha, T.; Gayen, S. First Molecular Modeling Report on Novel Arylpyrimidine Kynurenine Monooxygenase Inhibitors through Multi-QSAR Analysis against Huntington’s Disease: A Proposal to Chemists! Bioorg. Med. Chem. Lett., 2016, 26, 5712-5718.
[108]
Hong, Y.; Zhao, T.; Li, X.J.; Li, S. Mutant Huntingtin Impairs BDNF Release from Astrocytes by Disrupting Conversion of Rab3a-GTP into Rab3a-GDP. J. Neurosci., 2016, 36, 8790-8801.
[109]
Xiang, L.; Peng, Q.; Hou, Z.; Cai, H.; Seredenin, T.; Arbez, N.; Zhu, S.; Sommers, K.; Qian, J.; Zhang, J.; Mori, S.; Yang, X.W.; Tamashiro, K.L.K.; Aja, S.; Moran, T.H. Luthi-, R.; Martin, B.; Maudsley, S.; Mattson, M.P.; Cichewicz, R.H. Neuroprotective Role of SIRT1 in Mammalian Models of Huntington’s Disease through Activation of Multiple SIRT1 Targets. Nat. Med., 2015, 18, 153-158.
[110]
Johri, A.; Chandra, A.; Beal, M.F. PGC-1α, Mitochondrial Dysfunction, and Huntington’s Disease. Free Radic. Biol. Med., 2013, 62, 37-46.
[111]
Pagadala, N.S.; Bjorndahl, T.C.; Blinov, N.; Kovalenko, A.; Wishart, D.S. Molecular Docking of Thiamine Reveals Similarity in Binding Properties between the Prion Protein and Other Thiamine-Binding Proteins. J. Mol. Model., 2013, 19, 5225-5235.
[112]
George Priya Doss, C.; Rajith, B.; Rajasekaran, R.; Srajan, J.; Nagasundaram, N.; Debajyoti, C. in silico Analysis of Prion Protein Mutants: A Comparative Study by Molecular Dynamics Approach. Cell Biochem. Biophys., 2013, 67, 1307-1318.
[113]
Geschwind, M.D. Prion Diseases. Continuum (Minneap. Minn.), 2015, 21, 1612-1638.
[114]
Martins, V.R. A Receptor for Infectious and Cellular Prion Protein. Braz. J. Med. Biol. Res., 1999, 32, 853-859.
[115]
McDermott, C.J.; Shaw, P.J. Diagnosis and Management of Motor Neurone Disease. BMJ, 2008, 336, 658-662.
[116]
Kolb, S.J.; Kissel, J.T. Spinal Muscular Atrophy. Neurol. Clin., 2015, 33, 831-846.
[117]
Nance, J.R. Spinal Muscular Atrophy. Continuum (Minneap. Minn.), 2020, 26, 1348-1368.
[118]
D’Amico, A.; Eugenio, M.; Tiziano, F.D.; Bertini, E. Spinal Muscular Atrophy. Orphanet J. Rare Dis., 2011, 6, 1-10.
[119]
Arnold, W.D.; Kassar, D.; Kissel, J.T. Spinal Muscular Atrophy: Diagnosis and Management in a New Therapeutic Era. Muscle Nerve, 2015, 51, 157-167.
[120]
Cicardi, M.E.; Cristofani, R.; Crippa, V.; Ferrari, V.; Tedesco, B.; Casarotto, E.; Chierichetti, M.; Galbiati, M.; Piccolella, M.; Messi, E.; Carra, S.; Pennuto, M.; Rusmini, P.; Poletti, A. Autophagic and Proteasomal Mediated Removal of Mutant Androgen Receptor in Muscle Models of Spinal and Bulbar Muscular Atrophy. Front. Endocrinol. (Lausanne), 2019, 10, 1-14.
[121]
Borg, R.; Cauchi, R.J. Gemins: Potential Therapeutic Targets for Spinal Muscular Atrophy? Front. Neurosci., 2014, 8, 1-7.
[122]
Klockgether, T.; Mariotti, C.; Paulson, H.L. Spinocerebellar Ataxia. Nat. Rev. Dis. Primers, 2019, 5, 1-21.
[123]
Disease at a Glance., https://rarediseases.info.nih.gov/diseases/10748/spinocerebellar-ataxia
[124]
Kumar, S.; Tyagi, Y.K.; Kumar, M.; Kumar, S. Synthesis of novel 4-Methylthiocoumarin and comparison with conventional coumarin derivative as a multi-target-directed ligand in Alzheimer’s Disease. Biotech., 2010, 2010.
[125]
Sang, Z.; Wang, K.; Shi, J.; Cheng, X.; Zhu, G.; Wei, R.; Ma, Q.; Yu, L.; Zhao, Y.; Tan, Z.; Liu, W. Apigenin-Rivastigmine Hybrids as Multi-Target-Directed Liagnds for the Treatment of Alzheimer’s Disease. Eur. J. Med. Chem., 2020, 187111958
[126]
Chowdhury, S.; Kumar, S. Inhibition of BACE1, MAO-B, Cholinesterase Enzymes, and Anti-Amyloidogenic Potential of Selected Natural Phytoconstituents: Multi-Target-Directed Ligand Approach. J. Food Biochem., 2020, 1-21.
[127]
Haghighijoo, Z.; Akrami, S.; Saeedi, M.; Zonouzi, A.; Iraji, A.; Larijani, B.; Fakherzadeh, H.; Sharifi, F.; Arzaghi, S.M.; Mahdavi, M.; Edraki, N. N-Cyclohexylimidazo[1,2-a]Pyridine Derivatives as Multi-Target-Directed Ligands for Treatment of Alzheimer’s Disease. Bioorg. Chem., 2020, 103104146
[128]
Hao, F.; Feng, Y. Biological Evaluation of Naturally Occurring Bulbocodin D as a Potential Multi-Target Agent for Alzheimer’s Disease. Brain Res. Bull., 2020, 165, 48-55.
[129]
Jiang, X.; Zhou, J.; Wang, Y.; Chen, L.; Duan, Y.; Huang, J.; Liu, C.; Chen, Y.; Liu, W.; Sun, H.; Feng, F.; Qu, W. Rational Design and Biological Evaluation of a New Class of Thiazolopyridyl Tetrahydroacridines as Cholinesterase and GSK-3 Dual Inhibitors for Alzheimer’s Disease. Eur. J. Med. Chem., 2020, 207112751
[130]
Lima, J.A.; Thiago, T.W.; da Fonseca, A.C.C.; do Amaral, R.F.; Nascimento, M. do D.S.B.; Santos-Filho, O.A.; de Miranda, A.L.P.; Ferreira Neto, D.C.; Lima, F.R.S.; Hamerski, L.; Tinoco, L.W. Geissoschizoline, a Promising Alkaloid for Alzheimer’s Disease: Inhibition of Human Cholinesterases, Anti-Inflammatory Effects and Molecular Docking. Bioorg. Chem., 2020, 104104215
[131]
Oddsson, S.; Kowal, N.M.; Ahring, P.K.; Olafsdottir, E.S.; Balle, T. Structure-Based Discovery of Dual-Target Hits for Acetylcholinesterase and the A7 Nicotinic Acetylcholine Receptors: in silico Studies and in vitro Confirmation. Molecules, 2020, 25, 1-20.
[132]
Sobolova, K.; Hrabinova, M.; Hepnarova, V.; Kucera, T.; Kobrlova, T.; Benkova, M.; Janockova, J.; Dolezal, R.; Prchal, L.; Benek, O.; Mezeiova, E.; Jun, D.; Soukup, O.; Korabecny, J. Discovery of Novel Berberine Derivatives with Balanced Cholinesterase and Prolyl Oligopeptidase Inhibition Profile. Eur. J. Med. Chem., 2020, 203112593
[133]
Yu, Z.; Dong, W.; Wu, S.; Shen, J.; Zhao, W.; Ding, L.; Liu, J.; Zheng, F. Identification of Ovalbumin-Derived Peptides as Multi-Target Inhibitors of AChE, BChE, and BACE1. J. Sci. Food Agric., 2020, 100, 2648-2655.
[134]
Zhu, G.; Wang, K.; Shi, J.; Zhang, P.; Yang, D.; Fan, X.; Zhang, Z.; Liu, W.; Sang, Z. The Development of 2-Acetylphenol-Donepezil Hybrids as Multifunctional Agents for the Treatment of Alzheimer’s Disease. Bioorg. Med. Chem. Lett., 2019, 29126625
[135]
Riazimontazer, E.; Sadeghpour, H.; Nadri, H.; Sakhteman, A.; Tüylü Küçükkılınç, T.; Miri, R.; Edraki, N. Design, Synthesis and Biological Activity of Novel Tacrine-Isatin Schiff Base Hybrid Derivatives. Bioorg. Chem., 2019, 89103006
[136]
Oukoloff, K.; Coquelle, N.; Bartolini, M.; Naldi, M.; Le Guevel, R.; Bach, S.; Josselin, B.; Ruchaud, S.; Catto, M.; Pisani, L.; Denora, N.; Iacobazzi, R.M.; Silman, I.; Sussman, J.L.; Buron, F.; Colletier, J.P.; Jean, L.; Routier, S.; Renard, P.Y. Design, Biological Evaluation and X-Ray Crystallography of Nanomolar Multifunctional Ligands Targeting Simultaneously Acetylcholinesterase and Glycogen Synthase Kinase-3. Eur. J. Med. Chem., 2019, 168, 58-77.
[137]
Panche, A.N.; Chandra, S.; Diwan, A.D. Multi-Target β-Protease Inhibitors from Andrographis Paniculata: in silico and in vitro Studies. Plants, 2019, 8.
[138]
Kohelová, E.; Peřinová, R.; Maafi, N.; Korábečný, J.; Hulcová, D.; Maříková, J.; Kučera, T.; González, L.M.; Hrabinova, M.; Vorčáková, K.; Nováková, L.; De Simone, A.; Havelek, R.; Cahlíková, L. Derivatives of the β-Crinane Amaryllidaceae Alkaloid Haemanthamine as Multi-Target Directed Ligands for Alzheimer’s Disease. Molecules, 2019, 24.
[139]
Lee, J.; Jun, M. Dual BACE1 and Cholinesterase Inhibitory Effects of Phlorotannins from Ecklonia Cava-an in vitro and in silico Study. Mar. Drugs, 2019, 17, 1-15.
[140]
Mazumder, M.K.; Choudhury, S. Tea Polyphenols as Multi-Target Therapeutics for Alzheimer’s Disease: An in silico Study. Med. Hypotheses, 2019, 125, 94-99.
[141]
Kaur, A.; Mann, S.; Kaur, A.; Priyadarshi, N.; Goyal, B.; Singhal, N.K.; Goyal, D. Multi-Target-Directed Triazole Derivatives as Promising Agents for the Treatment of Alzheimer’s Disease. Bioorg. Chem., 2019, 87, 572-584.
[142]
Ghamari, N.; Dastmalchi, S.; Zarei, O.; Arias-Montaño, J.A.; Reiner, D.; Ustun-Alkan, F.; Stark, H.; Hamzeh-Mivehroud, M. in silico and in vitro Studies of Two Non-Imidazole Multiple Targeting Agents at Histamine H3 Receptors and Cholinesterase Enzymes. Chem. Biol. Drug Des., 2020, 95, 279-290.
[143]
Fronza, M.G.; Baldinotti, R.; Martins, M.C.; Goldani, B.; Dalberto, B.T.; Kremer, F.S.; Begnini, K.; Pinto, L. da S.; Lenardão, E.J.; Seixas, F.K.; Collares, T.; Alves, D.; Savegnago, L. Rational Design, Cognition and Neuropathology Evaluation of QTC-4-MeOBnE in a Streptozotocin-Induced Mouse Model of Sporadic Alzheimer’s Disease. Sci. Rep., 2019, 9, 1-14.
[144]
AlFadly, E.D.; Elzahhar, P.A.; Tramarin, A.; Elkazaz, S.; Shaltout, H.; Abu-Serie, M.M.; Janockova, J.; Soukup, O.; Ghareeb, D.A.; El-Yazbi, A.F.; Rafeh, R.W.; Bakkar, N.M.Z.; Kobeissy, F.; Iriepa, I.; Moraleda, I.; Saudi, M.N.S.; Bartolini, M.; Belal, A.S.F. Tackling Neuroinflammation and Cholinergic Deficit in Alzheimer’s Disease: Multi-Target Inhibitors of Cholinesterases, Cyclooxygenase-2 and 15-Lipoxygenase. Eur. J. Med. Chem., 2019, 167, 161-186.
[145]
Eslami, M.; Nezafat, N.; Negahdaripour, M.; Ghasemi, Y. Computational Approach to Suggest a New Multi-Target-Directed Ligand as a Potential Medication for Alzheimer’s Disease. J. Biomol. Struct. Dyn., 2019, 37, 4825-4839.
[146]
Yang, G.X.; Huang, Y.; Zheng, L.L.; Zhang, L.; Su, L.; Wu, Y.H.; Li, J.; Zhou, L.C.; Huang, J.; Tang, Y.; Wang, R.; Ma, L. Design, Synthesis and Evaluation of Diosgenin Carbamate Derivatives as Multitarget Anti-Alzheimer’s Disease Agents. Eur. J. Med. Chem., 2020, 187111913
[147]
Lan, J.S.; Zeng, R.F.; Jiang, X.Y.; Hou, J. wei; Liu, Y.; Hu, Z.H.; Li, H.X.; Li, Y.; Xie, S.S.; Ding, Y.; Zhang, T. Design, Synthesis and Evaluation of Novel Ferulic Acid Derivatives as Multi-Target-Directed Ligands for the Treatment of Alzheimer’s Disease. Bioorg. Chem., 2020, 94103413
[148]
Gabr, M.T.; Abdel-Raziq, M.S. Design and Synthesis of Donepezil Analogues as Dual AChE and BACE-1 Inhibitors. Bioorg. Chem., 2018, 80, 245-252.
[149]
Reis, J.; Cagide, F.; Valencia, M.E.; Teixeira, J.; Bagetta, D.; Pérez, C.; Uriarte, E.; Oliveira, P.J.; Ortuso, F.; Alcaro, S.; Rodríguez-Franco, M.I.; Borges, F. Multi-Target-Directed Ligands for Alzheimer’s Disease: Discovery of Chromone-Based Monoamine Oxidase/Cholinesterase Inhibitors. Eur. J. Med. Chem., 2018, 158, 781-800.
[150]
Panek, D.; Wiȩckowska, A.; Pasieka, A.; Godyń, J.; Jończyk, J.; Bajda, M.; Knez, D.; Gobec, S.; Malawska, B. Design, Synthesis, and Biological Evaluation of 2-(Benzylamino-2-Hydroxyalkyl)Isoindoline-1,3-Diones Derivatives as Potential Disease-Modifying Multifunctional Anti-Alzheimer Agents. Molecules, 2018, 23, 1-15.
[151]
Lee, S.; Youn, K.; Lim, G.T.; Lee, J.; Jun, M. in silico Docking and in vitro Approaches towards BACE1 and Cholinesterases Inhibitory Effect of Citrus Flavanones. Molecules, 2018, 23, 1-12.
[152]
Zhu, J.; Yang, H.; Chen, Y.; Lin, H.; Li, Q.; Mo, J.; Bian, Y.; Pei, Y.; Sun, H. Synthesis, Pharmacology and Molecular Docking on Multifunctional Tacrine-Ferulic Acid Hybrids as Cholinesterase Inhibitors against Alzheimer’s Disease. J. Enzyme Inhib. Med. Chem., 2018, 33, 496-506.
[153]
Hepnarova, V.; Korabecny, J.; Matouskova, L.; Jost, P.; Muckova, L.; Hrabinova, M.; Vykoukalova, N.; Kerhartova, M.; Kucera, T.; Dolezal, R.; Nepovimova, E.; Spilovska, K.; Mezeiova, E.; Pham, N.L.; Jun, D.; Staud, F.; Kaping, D.; Kuca, K.; Soukup, O. The Concept of Hybrid Molecules of Tacrine and Benzyl Quinolone Carboxylic Acid (BQCA) as Multifunctional Agents for Alzheimer’s Disease. Eur. J. Med. Chem., 2018, 150, 292-306.
[154]
Ambure, P.; Bhat, J.; Puzyn, T.; Roy, K. Identifying Natural Compounds as Multi-Target-Directed Ligands against Alzheimer’s Disease: An in silico Approach; , 2019, Vol. 37, .
[155]
Sarıkaya, G.; Çoban, G.; Parlar, S.; Tarikogullari, A.H.; Armagan, G.; Erdoğan, M.A.; Alptüzün, V.; Alpan, A.S. Multifunctional Cholinesterase Inhibitors for Alzheimer’s Disease: Synthesis, Biological Evaluations, and Docking Studies of o/p-Propoxyphenylsubstituted-1H-Benzimidazole Derivatives. Arch. Pharm. (Weinheim), 2018, 351, 1-18.
[156]
Yang, H.L.; Cai, P.; Liu, Q.H.; Yang, X.L.; Fang, S.Q.; Tang, Y.W.; Wang, C.; Wang, X.B.; Kong, L.Y. Design, Synthesis, and Evaluation of Salicyladimine Derivatives as Multitarget-Directed Ligands against Alzheimer’s Disease. Bioorg. Med. Chem., 2017, 25, 5917-5928.
[157]
Deng, Y.H.; Wang, N.N.; Zou, Z.X.; Zhang, L.; Xu, K.P.; Chen, A.F.; Cao, D.S.; Tan, G.S. Multi-Target Screening and Experimental Validation of Natural Products from Selaginella Plants against Alzheimer’s Disease. Front. Pharmacol., 2017, 8, 1-11.
[158]
Czarnecka, K.; Girek, M.; Maciejewska, K.; Skibiński, R.; Jończyk, J.; Bajda, M.; Kabziński, J.; Sołowiej, P.; Majsterek, I.; Szymański, P. New Cyclopentaquinoline Hybrids with Multifunctional Capacities for the Treatment of Alzheimer’s Disease. J. Enzyme Inhib. Med. Chem., 2018, 33, 158-170.
[159]
Fereidoonnezhad, M.; Mostoufi, A.; Eskandari, M.; Zali, S.; Aliyan, F. Multitarget Drug Design, Molecular Docking and PLIF Studies of Novel Tacrine-Coumarin Hybrids for the Treatment of Alzheimer’s Disease. Iran. J. Pharm. Res., 2018, 17, 1217-1228.
[160]
Horton, W.; Sood, A.; Peerannawar, S.; Kugyela, N.; Kulkarni, A.; Tulsan, R.; Tran, C.D.; Soule, J.; Biochemistry, C. HHS Public Access., 2018, 27, 232-236.
[161]
Xie, H.; Wen, H.; Zhang, D.; Liu, L.; Liu, B.; Liu, Q.; Jin, Q.; Ke, K.; Hu, M.; Chen, X. Designing of Dual Inhibitors for GSK-3β and CDK5: Virtual Screening and in vitro Biological Activities Study. Oncotarget, 2017, 8, 18118-18128.
[162]
Zhao, X.; Gong, D.; Jiang, Y.; Guo, D.; Zhu, Y.; Deng, Y. Multipotent AChE and BACE-1 Inhibitors for the Treatment of Alzheimer’s Disease: Design, Synthesis and Bio-Analysis of 7-Amino-1,4-Dihydro-2H-Isoquilin-3-One Derivates. Eur. J. Med. Chem., 2017, 138, 738-747.
[163]
Jyothi, P.; Yellamma, K. Molecular Docking Studies on the Therapeutic Targets of Alzheimer’s Disease (AChE and BChE) Using Natural Bioactive Alkaloids. Int. J. Pharm. Pharm. Sci., 2016, 8, 108-112.
[164]
Mishra, C.B.; Kumari, S.; Manral, A.; Prakash, A.; Saini, V.; Lynn, A.M.; Tiwari, M. Design, Synthesis, in-silico and Biological Evaluation of Novel Donepezil Derivatives as Multi-Target-Directed Ligands for the Treatment of Alzheimer’s Disease. Eur. J. Med. Chem., 2017, 125, 736-750.
[165]
Xie, S.S.; Lan, J.S.; Wang, X.; Wang, Z.M.; Jiang, N.; Li, F.; Wu, J.J.; Wang, J.; Kong, L.Y. Design, Synthesis and Biological Evaluation of Novel Donepezil-Coumarin Hybrids as Multi-Target Agents for the Treatment of Alzheimer’s Disease. Bioorg. Med. Chem., 2016, 24, 1528-1539.
[166]
Xie, S.S.; Wang, X.; Jiang, N.; Yu, W.; Wang, K.D.G.; Lan, J.S.; Li, Z.R.; Kong, L.Y. Multi-Target Tacrine-Coumarin Hybrids: Cholinesterase and Monoamine Oxidase B Inhibition Properties against Alzheimer’s Disease. Eur. J. Med. Chem., 2015, 95, 153-165.
[167]
Korabecny, J.; Andrs, M.; Nepovimova, E.; Dolezal, R.; Babkova, K.; Horova, A.; Malinak, D.; Mezeiova, E.; Gorecki, L.; Sepsova, V.; Hrabinova, M.; Soukup, O.; Jun, D.; Kuca, K. 7-Methoxytacrine-p-Anisidine Hybrids as Novel Dual Binding Site Acetylcholinesterase Inhibitors for Alzheimer’s Disease Treatment. Molecules, 2015, 20, 22084-22101.
[168]
Bansode, S.B.; Jana, A.K.; Batkulwar, K.B.; Warkad, S.D.; Joshi, R.S.; Sengupta, N.; Kulkarni, M.J. Molecular Investigations of Protriptyline as a Multi-Target Directed Ligand in Alzheimer’s Disease. PLoS One, 2014, 9.
[169]
Wang, L.; Esteban, G.; Ojima, M.; Bautista-Aguilera, O.M.; Inokuchi, T.; Moraleda, I.; Iriepa, I.; Samadi, A.; Youdim, M.B.H.; Romero, A.; Soriano, E.; Herrero, R.; Fernández Fernández, A.P. Ricardo-Martínez-Murillo; Marco-Contelles, J.; Unzeta, M. 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, 543-561.
[170]
Liu, J.; Qiu, J.; Wang, M.; Wang, L.; Su, L.; Gao, J.; Gu, Q.; Xu, J.; Huang, S.L.; Gu, L.Q.; Huang, Z.S.; Li, D. Synthesis and Characterization of 1H-Phenanthro[9,10-d]Imidazole Derivatives as Multifunctional Agents for Treatment of Alzheimer’s Disease. Biochim. Biophys. Acta, Gen. Subj., 2014, 1840, 2886-2903.
[171]
González-Naranjo, P.; Pérez-Macias, N.; Campillo, N.E.; Pérez, C.; Arán, V.J.; Girón, R.; Sánchez-Robles, E.; Martín, M.I.; Gómez-Cañas, M.; García-Arencibia, M.; Fernández-Ruiz, J.; Páez, J.A. Cannabinoid Agonists Showing BChE Inhibition as Potential Therapeutic Agents for Alzheimer’s Disease. Eur. J. Med. Chem., 2014, 73, 56-72.
[172]
Spilovska, K.; Korabecny, J.; Kral, J.; Horova, A.; Musilek, K.; Soukup, O.; Drtinova, L.; Gazova, Z.; Siposova, K.; Kuca, K. 7-Methoxytacrine-Adamantylamine Heterodimers as Cholinesterase Inhibitors in Alzheimer’s Disease Treatment - Synthesis, Biological Evaluation and Molecular Modeling Studies. Molecules, 2013, 18, 2397-2418.
[173]
Huang, W.; Tang, L.; Shi, Y.; Huang, S.; Xu, L.; Sheng, R.; Wu, P.; Li, J.; Zhou, N.; Hu, Y. Searching for the Multi-Target-Directed Ligands against Alzheimer’s Disease: Discovery of Quinoxaline-Based Hybrid Compounds with AChE, H 3R and BACE 1 Inhibitory Activities. Bioorg. Med. Chem., 2011, 19, 7158-7167.
[174]
Yang, A.; Yu, Q.; Ju, H.; Song, L.; Kou, X.; Shen, R. Design, Synthesis and Biological Evaluation of Xanthone Derivatives for Possible Treatment of Alzheimer’s Disease Based on Multi-Target Strategy. Chem. Biodivers., 2020, 17.
[175]
Dhamodharan, G.; Mohan, C.G. Machine Learning Models for Predicting the Activity of AChE and BACE1 Dual Inhibitors for the Treatment of Alzheimer’s Disease. Mol. Divers., 2022, 26, 1501-1517.
[176]
Gao, H.; Jiang, Y.; Zhan, J.; Sun, Y. Pharmacophore-Based Drug Design of AChE and BChE Dual Inhibitors as Potential Anti-Alzheimer’s Disease Agents. Bioorg. Chem., 2021, 114105149
[177]
Ojo, O.A.; Ojo, A.B.; Okolie, C.; Nwakama, M-A.C.; Iyobhebhe, M.; Evbuomwan, I.O.; Nwonuma, C.O.; Maimako, R.F.; Adegboyega, A.E.; Taiwo, O.A.; Alsharif, K.F.; Batiha, G.E-S. Deciphering the Interactions of Bioactive Compounds in Selected Traditional Medicinal Plants against Alzheimer’s Diseases via Pharmacophore Modeling, Auto-QSAR, and Molecular Docking Approaches. Molecules, 2021, 26, 1996.
[178]
Brunetti, L.; Leuci, R.; Carrieri, A.; Catto, M.; Occhineri, S.; Vinci, G.; Gambacorta, L.; Baltrukevich, H.; Chaves, S.; Laghezza, A.; Altomare, C.D.; Tortorella, P.; Santos, M.A.; Loiodice, F.; Piemontese, L. Structure-Based Design of Novel Donepezil-like Hybrids for a Multi-Target Approach to the Therapy of Alzheimer’s Disease. Eur. J. Med. Chem., 2022, 237114358
[179]
Leuci, R.; Brunetti, L.; Laghezza, A.; Piemontese, L.; Carrieri, A.; Pisani, L.; Tortorella, P.; Catto, M.; Loiodice, F. A New Series of Aryloxyacetic Acids Endowed with Multi-Target Activity towards Peroxisome Proliferator-Activated Receptors (PPARs), Fatty Acid Amide Hydrolase (FAAH), and Acetylcholinesterase (AChE). Molecules, 2022, 27, 958.
[180]
Paudel, P.; Park, S.E.; Seong, S.H.; Jung, H.A.; Choi, J.S. Bromophenols from Symphyocladia Latiuscula Target Human Monoamine Oxidase and Dopaminergic Receptors for the Management of Neurodegenerative Diseases. J. Agric. Food Chem., 2020, 68, 2426-2436.
[181]
Hagenow, J.; Hagenow, S.; Grau, K.; Khanfar, M.; Hefke, L.; Proschak, E.; Stark, H. Reversible Small Molecule Inhibitors of MAO A and MAO B with Anilide Motifs. Drug Des. Devel. Ther., 2020, 14, 371-393.
[182]
Seong, S.H.; Paudel, P.; Choi, J.W.; Ahn, D.H.; Nam, T.J.; Jung, H.A.; Choi, J.S. Probing Multi-Target Action of Phlorotannins as New Monoamine Oxidase Inhibitors and Dopaminergic Receptor Modulators with the Potential for Treatment of Neuronal Disorders. Mar. Drugs, 2019, 17.
[183]
Jaiteh, M.; Zeifman, A.; Saarinen, M.; Svenningsson, P.; Bréa, J.; Loza, M.I.; Carlsson, J. Docking Screens for Dual Inhibitors of Disparate Drug Targets for Parkinson’s Disease. J. Med. Chem., 2018, 61, 5269-5278.
[184]
Khan, N.A.; Khan, I.; Abid, S.M.A.; Zaib, S.; Ibrar, A.; Andleeb, H.; Hameed, S.; Iqbal, J. Quinolinic Carboxylic Acid Derivatives as Potential Multi-Target Compounds for Neurodegeneration: Monoamine Oxidase and Cholinesterase Inhibition. Med. Chem. (Los Angeles), 2017, 14, 74-85.
[185]
Koch, P.; Brunschweiger, A.; Namasivayam, V.; Ullrich, S.; Maruca, A.; Lazzaretto, B.; Küppers, P.; Hinz, S.; Hockemeyer, J.; Wiese, M.; Heer, J.; Alcaro, S.; Kiec-Kononowicz, K.; Müller, C.E. Probing Substituents in the 1- and 3-Position: Tetrahydropyrazino-Annelated Water-Soluble Xanthine Derivatives as Multi-Target Drugs with Potent Adenosine Receptor Antagonistic Activity. Front Chem., 2018, 6, 1-28.
[186]
Ribaudo, G.; Zanforlin, E.; Canton, M.; Bova, S.; Zagotto, G. Preliminary Studies of Berberine and Its Semi-Synthetic Derivatives as a Promising Class of Multi-Target Anti-Parkinson Agents. Nat. Prod. Res., 2018, 32, 1395-1401.
[187]
Meng, X-Y.; Zhang, H-X.; Mezei, M.; Cui, M. Molecular Docking: A Powerful Approach for Structure-Based Drug Discovery. Curr. Comput. Aided. Drug Des., 2011, 7, 146-157.
[188]
Matore, B.W.; Banjare, P.; Singh, J.; Roy, P.P. in silico Selectivity Modeling of Pyridine and Pyrimidine Based CYP11B1 and CYP11B2 Inhibitors: A Case Study. J. Mol. Graph. Model., 2022, 116108238
[189]
Lambrinidis, G.; Tsantili-Kakoulidou, A. Challenges with Multi-Objective QSAR in Drug Discovery. Expert Opin. Drug Discov., 2018, 13, 851-859.
[190]
Zanni, R.; Gálvez-Llompart, M.; Gálvez, J. G.-D.R. QSAR Multi-Target in Drug Discovery: A Review. Curr Comput Aided Drug Des., 2014, 10, 129-136.
[191]
Ambure, P.; Halder, A.K.; González Díaz, H.; Cordeiro, M.N.D.S. QSAR-Co: An Open Source Software for Developing Robust Multitasking or Multitarget Classification-Based QSAR Models. J. Chem. Inf. Model., 2019, 59, 2538-2544.
[192]
Halder, A.K.; Dias Soeiro Cordeiro, M.N. QSAR-Co-X: An Open Source Toolkit for Multitarget QSAR Modelling. J. Cheminform., 2021, 13, 29.
[193]
Kier, L.B. Molecular Orbital Calculation of Preferred Conformations of Acetylcholine, Muscarine, and Muscarone. Mol. Pharmacol., 1967, 3, 487-494.
[194]
Voet, A.; Qing, X.; Lee, X.Y.; De Raeymaecker, J.; Tame, J.; Zhang, K.; De Maeyer, M. Pharmacophore Modeling: Advances, Limitations, and Current Utility in Drug Discovery. J. Receptor Ligand Channel Res., 2014, 2014(7), 81-92.
[195]
Fischer, T.; Gazzola, S.; Riedl, R. Approaching target selectivity by de novo drug design. Expert Opin. Drug Discov., 2019, 14, 791-803.
[196]
Shang, E.; Yuan, Y.; Chen, X.; Liu, Y.; Pei, J.; Lai, L. De Novo Design of Multitarget Ligands with an Iterative Fragment-Growing Strategy. J. Chem. Inf. Model., 2014, 54, 1235-1241.
[197]
Wale, N.; Karypis, G. Target Fishing for Chemical Compounds Using Target-Ligand Activity Data and Ranking Based Methods. J. Chem. Inf. Model., 2009, 49, 2190-2201.
[198]
Teich, A.F.; Arancio, O. Is the Amyloid Hypothesis of Alzheimer’s Disease Therapeutically Relevant? Biochem. J., 2012, 446, 165-177.
[199]
Sahu, P.K.; Tiwari, P.; Prusty, S.K. CHAPTER 7 past and present Alzheimer ’ s Disease drug development. 2019.
[200]
Koutsoukas, A.; Simms, B.; Kirchmair, J.; Bond, P.J.; Whitmore, A.V.; Zimmer, S.; Young, M.P.; Jenkins, J.L.; Glick, M.; Glen, R.C.; Bender, A. From in silico Target Prediction to Multi-Target Drug Design: Current Databases, Methods and Applications. J. Proteomics, 2011, 74, 2554-2574.
[201]
Ma, X.H.; Shi, Z.; Tan, C.; Jiang, Y.; Go, M.L.; Low, B.C.; Chen, Y.Z. in-silico Approaches to Multi-Target Drug Discovery Computer Aided Multi-Target Drug Design, Multi-Target Virtual Screening. Pharm. Res., 2010, 27, 739-749.
[202]
Sehgal, S.A.; Hammad, M.A.; Tahir, R.A.; Akram, H.N.; Ahmad, F. Current Therapeutic Molecules and Targets in Neurodegenerative Diseases Based on in silico Drug Design. Curr. Neuropharmacol., 2018, 16, 649-663.
[203]
Matore, B.W.; Banjare, P.; Guria, T.; Roy, P.P.; Singh, J. Oxadiazole Derivatives: Histone Deacetylase Inhibitors in Anticancer Therapy and Drug Discovery. Eur. J. Med. Chem. Reports, 2022, 5100058
[204]
Matore, B.W.; Roy, P.P.; Singh, J. Discovery of Novel VEGFR2-TK Inhibitors by Phthalimide Pharmacophore Based Virtual Screening, Molecular Docking, MD Simulation and DFT. J. Biomol. Struct. Dyn., 2023, 1-22.
[205]
Glomb, T.; Wiatrak, B.; Gębczak, K.; Gębarowski, T.; Bodetko, D.; Czyżnikowska, Ż.; Świątek, P. New 1,3,4-Oxadiazole Derivatives of Pyridothiazine-1,1-Dioxide with Anti-Inflammatory Activity. Int. J. Mol. Sci., 2020, 21, 9122.
[206]
Chainoglou, E.; Siskos, A.; Pontiki, E.; Hadjipavlou-Litina, D. Hybridization of Curcumin Analogues with Cinnamic Acid Derivatives as Multi-Target Agents Against Alzheimer’s Disease Targets. Molecules, 2020, 25, 4958.
[207]
Ivasiv, V.; Albertini, C.; Gonçalves, A.E.; Rossi, M.; Bolognesi, M.L. Molecular Hybridization as a Tool for Designing Multitarget Drug Candidates for Complex Diseases. Curr. Top. Med. Chem., 2019, 19, 1694-1711.
[208]
Michalska, P.; Buendia, I.; Del Barrio, L.; Leon, R. Novel Multitarget Hybrid Compounds for the Treatment of Alzheimer’s Disease. Curr. Top. Med. Chem., 2017, 17, 1027-1043.
[209]
Matore, B.W.; Banjare, P.; Sarthi, A.S.; Roy, P.P.; Singh, J. Phthalimides Represent a Promising Scaffold for Multi-Targeted Anticancer Agents. ChemistrySelect, 2023, 8.
[210]
Roy, P.P.; Banjare, P.; Verma, S.; Singh, J. Acute Rat and Mouse Oral Toxicity Determination of Anticholinesterase Inhibitor Carbamate Pesticides: A QSTR Approach. Mol. Inform., 2019, 38, 1-17.
[211]
Banjare, P.; Singh, J.; Roy, P.P. Predictive Classification-Based QSTR Models for Toxicity Study of Diverse Pesticides on Multiple Avian Species. Environ. Sci. Pollut. Res. Int., 2021, 28, 17992-18003.

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