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Current Alzheimer Research

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Review Article

Donepezil Derivatives Targeting Amyloid-β Cascade in Alzheimer's Disease

Author(s): Eva Mezeiova, Katarina Chalupova, Eugenie Nepovimova, Lukas Gorecki, Lukas Prchal, David Malinak, Kamil Kuca, Ondrej Soukup and Jan Korabecny*

Volume 16, Issue 9, 2019

Page: [772 - 800] Pages: 29

DOI: 10.2174/1567205016666190228122956

Price: $65

Abstract

Alzheimer's Disease (AD) is a neurodegenerative disorder with an increasing impact on society. Because currently available therapy has only a short-term effect, a huge number of novel compounds are developed every year exploiting knowledge of the various aspects of AD pathophysiology. To better address the pathological complexity of AD, one of the most extensively pursued strategies by medicinal chemists is based on Multi-target-directed Ligands (MTDLs). Donepezil is one of the currently approved drugs for AD therapy acting as an acetylcholinesterase inhibitor. In this review, we have made an extensive literature survey focusing on donepezil-derived MTDL hybrids primarily targeting on different levels cholinesterases and amyloid beta (Aβ) peptide. The targeting includes direct interaction of the compounds with Aβ, AChE-induced Aβ aggregation, inhibition of BACE-1 enzyme, and modulation of biometal balance thus impeding Aβ assembly.

Keywords: Acetylcholinesterase, Alzheimer`s disease, amyloid-β, biometal, beta-secretase 1, butyrylcholinesterase, multitarget directed ligands, neuroprotection.

[1]
Karlawish J. Addressing the ethical, policy, and social challenges of preclinical Alzheimer disease. Neurology 77(15): 1487-93. (2011).
[http://dx.doi.org/10.1212/WNL.0b013e318232ac1a] [PMID: 21917767]
[2]
Burns A, Jacoby R, Levy R. Psychiatric phenomena in Alzheimer’s disease. I: Disorders of thought content. Br J Psychiatry 157(1): 72-76, 92-94. (1990).
[http://dx.doi.org/10.1192/bjp.157.1.72] [PMID: 2397365]
[3]
Holtzman DM, Morris JC, Goate AM. Alzheimer’s disease: the challenge of the second century. Sci Transl Med 3(77): 77sr1. (2011).
[http://dx.doi.org/10.1126/scitranslmed.3002369] [PMID: 21471435]
[4]
Maresova P, Klimova B, Novotny M, Kuca K. Alzheimer’s and Parkinson’s diseases: expected economic impact on europe-a call for a uniform european strategy. J Alzheimers Dis 54(3): 1123-33. (2016).
[http://dx.doi.org/10.3233/JAD-160484] [PMID: 27567862]
[5]
Marešová P, Mohelská H, Dolejš J, Kuča K. Socio-economic aspects of Alzheimer’s disease. Curr Alzheimer Res 12(9): 903-11. (2015).
[http://dx.doi.org/10.2174/156720501209151019111448] [PMID: 26510983]
[6]
Dickerson BC, Stoub TR, Shah RC, Sperling RA, Killiany RJ, Albert MS, et al. Alzheimer-signature MRI biomarker predicts AD dementia in cognitively normal adults. Neurology 76(16): 1395-402. (2011).
[http://dx.doi.org/10.1212/WNL.0b013e3182166e96] [PMID: 21490323]
[7]
Serrano-Pozo A, Frosch MP, Masliah E, Hyman BT. Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect Med 1(1)a006189 (2011).
[http://dx.doi.org/10.1101/cshperspect.a006189] [PMID: 22229116]
[8]
Querfurth HW, LaFerla FM. Alzheimer’s disease. N Engl J Med 362(4): 329-44. (2010).
[http://dx.doi.org/10.1056/NEJMra0909142] [PMID: 20107219]
[9]
Barage SH, Sonawane KD. Amyloid cascade hypothesis: pathogenesis and therapeutic strategies in Alzheimer’s disease. Neuropeptides 52: 1-18. (2015).
[http://dx.doi.org/10.1016/j.npep.2015.06.008] [PMID: 26149638]
[10]
Mesulam M, Guillozet A, Shaw P, Quinn B. Widely spread butyrylcholinesterase can hydrolyze acetylcholine in the normal and Alzheimer brain. Neurobiol Dis 9(1): 88-93. (2002).
[http://dx.doi.org/10.1006/nbdi.2001.0462] [PMID: 11848688]
[11]
Long JZ, Cravatt BF. The metabolic serine hydrolases and their functions in mammalian physiology and disease. Chem Rev 111(10): 6022-63. (2011).
[http://dx.doi.org/10.1021/cr200075y] [PMID: 21696217]
[12]
Contestabile A. The history of the cholinergic hypothesis. Behav Brain Res 221(2): 334-40. (2011).
[http://dx.doi.org/10.1016/j.bbr.2009.12.044] [PMID: 20060018]
[13]
Zemek F, Drtinova L, Nepovimova E, Sepsova V, Korabecny J, Klimes J, et al. Outcomes of Alzheimer’s disease therapy with acetylcholinesterase inhibitors and memantine. Expert Opin Drug Saf 13(6): 759-74. (2014).
[PMID: 24845946]
[14]
Shintani EY, Uchida KM. Donepezil: an anticholinesterase inhibitor for Alzheimer’s disease. Am J Health Syst Pharm 54(24): 2805-10. (1997).
[http://dx.doi.org/10.1093/ajhp/54.24.2805] [PMID: 9428950]
[15]
Doody RS, Cummings JL, Farlow MR. Reviewing the role of donepezil in the treatment of Alzheimer’s disease. Curr Alzheimer Res 9(7): 773-81. (2012).
[http://dx.doi.org/10.2174/156720512802455412] [PMID: 22175653]
[16]
Korabecny J, Zemek F, Soukup O, Spilovska K, Musilek K, Jun D, et al. Chapter 1 - Pharmacotherapy of Alzheimer’s Disease: Current State and Future Perspectives In: (Eds: Atta-ur-Rahman and Choudhary MI) Drug Design and Discovery in Alzheimer’s Disease Elsevier. 3-39. (2014).
[17]
Wan L, Lu J, Fu J, Huang J, Yang Q, Xin B, et al. Acetylcholinesterase inhibitor donepezil effects on plasma β-hydroxybutyrate levels in the treatment of Alzheimer’s disease. Curr Alzheimer Res 15(10): 917-27. (2018).
[http://dx.doi.org/10.2174/1567205015666180601091818] [PMID: 29852870]
[18]
Sabbagh MN, Farlow MR, Relkin N, Beach TG. Do cholinergic therapies have disease-modifying effects in Alzheimer’s disease? Alzheimers Dement 2(2): 118-25. (2006).
[http://dx.doi.org/10.1016/j.jalz.2006.02.001] [PMID: 19595868]
[19]
Sabbagh MN, Richardson S, Relkin N. Disease-modifying approaches to Alzheimer’s disease: challenges and opportunities-Lessons from donepezil therapy. Alzheimers Dement 4(1): S109-18. (2008).
[http://dx.doi.org/10.1016/j.jalz.2007.11.013] [PMID: 18631986]
[20]
Hardy JA, Higgins GA. Alzheimer’s disease: the amyloid cascade hypothesis. Science 256(5054): 184-5. (1992).
[http://dx.doi.org/10.1126/science.1566067] [PMID: 1566067]
[21]
Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol Med 8(6): 595-608. (2016).
[http://dx.doi.org/10.15252/emmm.201606210] [PMID: 27025652]
[22]
Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K. Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci USA 82(12): 4245-9. (1985).
[http://dx.doi.org/10.1073/pnas.82.12.4245] [PMID: 3159021]
[23]
Kang J, Lemaire HG, Unterbeck A, Salbaum JM, Masters CL, Grzeschik KH, et al. The precursor of Alzheimer’s disease amyloid A4 protein resembles a cell-surface receptor. Nature 325(6106): 733-6. (1987).
[http://dx.doi.org/10.1038/325733a0] [PMID: 2881207]
[24]
Turner PR, O’Connor K, Tate WP, Abraham WC. Roles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory. Prog Neurobiol 70(1): 1-32. (2003).
[http://dx.doi.org/10.1016/S0301-0082(03)00089-3] [PMID: 12927332]
[25]
Dawkins E, Small DH. Insights into the physiological function of the β-amyloid precursor protein: beyond Alzheimer’s disease. J Neurochem 129(5): 756-69. (2014).
[http://dx.doi.org/10.1111/jnc.12675] [PMID: 24517464]
[26]
Zhang X, Song W. The role of APP and BACE1 trafficking in APP processing and amyloid-β generation. Alzheimers Res Ther 5(5): 46. (2013).
[http://dx.doi.org/10.1186/alzrt211] [PMID: 24103387]
[27]
Nalivaeva NN, Turner AJ. The amyloid precursor protein: a biochemical enigma in brain development, function and disease. FEBS Lett 587(13): 2046-54. (2013).
[http://dx.doi.org/10.1016/j.febslet.2013.05.010] [PMID: 23684647]
[28]
LaFerla FM, Green KN, Oddo S. Intracellular amyloid-beta in Alzheimer’s disease. Nat Rev Neurosci 8(7): 499-509. (2007).
[http://dx.doi.org/10.1038/nrn2168] [PMID: 17551515]
[29]
Burdick D, Soreghan B, Kwon M, Kosmoski J, Knauer M, Henschen A, et al. Assembly and aggregation properties of synthetic Alzheimer’s A4/beta amyloid peptide analogs. J Biol Chem 267(1): 546-54. (1992).
[PMID: 1730616]
[30]
Roher AE, Lowenson JD, Clarke S, Woods AS, Cotter RJ, Gowing E, et al. beta-Amyloid-(1-42) is a major component of cerebrovascular amyloid deposits: implications for the pathology of Alzheimer disease. Proc Natl Acad Sci USA 90(22): 10836-40. (1993).
[http://dx.doi.org/10.1073/pnas.90.22.10836] [PMID: 8248178]
[31]
Portelius E, Price E, Brinkmalm G, Stiteler M, Olsson M, Persson R, et al. A novel pathway for amyloid precursor protein processing. Neurobiol Aging 32(6): 1090-8. (2011).
[http://dx.doi.org/10.1016/j.neurobiolaging.2009.06.002] [PMID: 19604603]
[32]
Praticò D. Evidence of oxidative stress in Alzheimer’s disease brain and antioxidant therapy: lights and shadows. Ann N Y Acad Sci 1147: 70-8. (2008).
[http://dx.doi.org/10.1196/annals.1427.010] [PMID: 19076432]
[33]
Sultana R, Mecocci P, Mangialasche F, Cecchetti R, Baglioni M, Butterfield DA. Increased protein and lipid oxidative damage in mitochondria isolated from lymphocytes from patients with Alzheimer’s disease: insights into the role of oxidative stress in Alzheimer’s disease and initial investigations into a potential biomarker for this dementing disorder. J Alzheimers Dis 24(1): 77-84. (2011).
[http://dx.doi.org/10.3233/JAD-2011-101425] [PMID: 21383494]
[34]
Lovell MA, Robertson JD, Teesdale WJ, Campbell JL, Markesbery WR. Copper, iron and zinc in Alzheimer’s disease senile plaques. J Neurol Sci 158(1): 47-52. (1998).
[http://dx.doi.org/10.1016/S0022-510X(98)00092-6] [PMID: 9667777]
[35]
Huang X, Moir RD, Tanzi RE, Bush AI, Rogers JT. Redox-active metals, oxidative stress, and Alzheimer’s disease pathology. Ann N Y Acad Sci 1012: 153-63. (2004).
[http://dx.doi.org/10.1196/annals.1306.012] [PMID: 15105262]
[36]
Halliwell B, Gutteridge JM. Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem J 219(1): 1-14. (1984).
[http://dx.doi.org/10.1042/bj2190001] [PMID: 6326753]
[37]
Lee HP, Zhu X, Casadesus G, Castellani RJ, Nunomura A, Smith MA, et al. Antioxidant approaches for the treatment of Alzheimer’s disease. Expert Rev Neurother 10(7): 1201-8. (2010).
[http://dx.doi.org/10.1586/ern.10.74] [PMID: 20586698]
[38]
Ansari UR. Challenges in designing therapeutic agents for treating Alzheimer’s disease-from serendipity to rationality (2014).
[39]
Spilovska K, Korabecny J, Nepovimova E, Dolezal R, Mezeiova E, Soukup O, et al. Multitarget tacrine hybrids with neuroprotective properties to confront Alzheimer’s disease. Curr Top Med Chem 17(9): 1006-26. (2017).
[http://dx.doi.org/10.2174/1568026605666160927152728] [PMID: 27697055]
[40]
Mezeiova E, Spilovska K, Nepovimova E, Gorecki L, Soukup O, Dolezal R, et al. Profiling donepezil template into multipotent hybrids with antioxidant properties. J Enzyme Inhib Med Chem 33(1): 583-606. (2018).
[http://dx.doi.org/10.1080/14756366.2018.1443326] [PMID: 29529892]
[41]
Unzeta M, Esteban G, Bolea I, Fogel WA, Ramsay RR, Youdim MB, et al. Multi-target directed donepezil-like ligands for Alzheimer’s disease. Front Neurosci 10: 205. (2016).
[http://dx.doi.org/10.3389/fnins.2016.00205] [PMID: 27252617]
[42]
Chakraborty S. Multi-potent natural scaffolds targeting amyloid cascade: in search of Alzheimer’s disease therapeutics. Curr Top Med Chem 17(31): 3336-48. (2017).
[http://dx.doi.org/10.2174/1568026618666180116122921] [PMID: 29345580]
[43]
Das S, Basu S. Multi-targeting strategies for Alzheimer’s disease therapeutics: pros and cons. Curr Top Med Chem 17(27): 3017-61. (2017).
[http://dx.doi.org/10.2174/1568026617666170707130652] [PMID: 28685694]
[44]
Grill JD, Cummings JL. Novel targets for Alzheimer’s disease treatment. Expert Rev Neurother 10(5): 711-28. (2010).
[http://dx.doi.org/10.1586/ern.10.29] [PMID: 20420492]
[45]
Hughes RE, Nikolic K, Ramsay RR. One for all? hitting multiple Alzheimer’s disease targets with one drug. Front Neurosci 10: 177. (2016).
[http://dx.doi.org/10.3389/fnins.2016.00177] [PMID: 27199640]
[46]
Claeysen S, Bockaert J, Giannoni P. Serotonin: a new hope in Alzheimer’s disease? ACS Chem Neurosci 6(7): 940-3. (2015).
[http://dx.doi.org/10.1021/acschemneuro.5b00135] [PMID: 26011650]
[47]
Więckowska A, Wichur T, Godyń J, Bucki A, Marcinkowska M, Siwek A, et al. Novel multitarget-directed ligands aiming at symptoms and causes of Alzheimer’s disease. ACS Chem Neurosci 9(5): 1195-214. (2018).
[http://dx.doi.org/10.1021/acschemneuro.8b00024] [PMID: 29384656]
[48]
Alvarez A, Opazo C, Alarcón R, Garrido J, Inestrosa NC. Acetylcholinesterase promotes the aggregation of amyloid-beta-peptide fragments by forming a complex with the growing fibrils. J Mol Biol 272(3): 348-61. (1997).
[http://dx.doi.org/10.1006/jmbi.1997.1245] [PMID: 9325095]
[49]
Hawkes CA, Ng V, McLaurin J. Small molecule inhibitors of Aβ-aggregation and neurotoxicity. Drug Dev Res 70(2): 111-24. (2009).
[http://dx.doi.org/10.1002/ddr.20290]
[50]
Inestrosa NC, Alvarez A, Pérez CA, Moreno RD, Vicente M, Linker C, et al. Acetylcholinesterase accelerates assembly of amyloid-beta-peptides into Alzheimer’s fibrils: possible role of the peripheral site of the enzyme. Neuron 16(4): 881-91. (1996).
[http://dx.doi.org/10.1016/S0896-6273(00)80108-7] [PMID: 8608006]
[51]
Camps P, Formosa X, Galdeano C, Gómez T, Muñoz-Torrero D, Ramírez L, et al. Tacrine-based dual binding site acetylcholinesterase inhibitors as potential disease-modifying anti-Alzheimer drug candidates. Chem Biol Interact 187(1-3): 411-5. (2010).
[http://dx.doi.org/10.1016/j.cbi.2010.02.013] [PMID: 20167211]
[52]
Camps P, Formosa X, Galdeano C, Gómez T, Muñoz-Torrero D, Scarpellini M, et al. Novel donepezil-based inhibitors of acetyl- and butyrylcholinesterase and acetylcholinesterase-induced beta-amyloid aggregation. J Med Chem 51(12): 3588-98. (2008).
[http://dx.doi.org/10.1021/jm8001313] [PMID: 18517184]
[53]
Alonso D, Dorronsoro I, Rubio L, Muñoz P, García-Palomero E, Del Monte M, et al. Donepezil-tacrine hybrid related derivatives as new dual binding site inhibitors of AChE. Bioorg Med Chem 13(24): 6588-97. (2005).
[http://dx.doi.org/10.1016/j.bmc.2005.09.029] [PMID: 16230018]
[54]
Kryger G, Silman I, Sussman JL. Structure of acetylcholinesterase complexed with E2020 (Aricept): implications for the design of new anti-Alzheimer drugs. Struct Lond Engl 7(3): 297-307. (1999).
[55]
Taylor P, Lappi S. Interaction of fluorescence probes with acetylcholinesterase. The site and specificity of propidium binding. Biochemistry 14(9): 1989-97. (1975).
[http://dx.doi.org/10.1021/bi00680a029] [PMID: 1125207]
[56]
Piazzi L, Rampa A, Bisi A, et al. 3-(4-[[Benzyl(methyl)amino]methyl]phenyl)-6,7-dimethoxy-2H-2-chromenone (AP2238) inhibits both acetylcholinesterase and acetylcholinesterase-induced beta-amyloid aggregation: a dual function lead for Alzheimer’s disease therapy. J Med Chem 46(12): 2279-82. (2003).
[http://dx.doi.org/10.1021/jm0340602] [PMID: 12773032]
[57]
Anand P, Singh B, Singh N. A review on coumarins as acetylcholinesterase inhibitors for Alzheimer’s disease. Bioorg Med Chem 2012; 20(3): 1175-80.
[http://dx.doi.org/10.1016/j.bmc.2011.12.042] [PMID: 22257528]
[58]
Brühlmann C, Ooms F, Carrupt PA, Testa B, Catto M, Leonetti F, et al. Coumarins derivatives as dual inhibitors of acetylcholinesterase and monoamine oxidase. J Med Chem 44(19): 3195-8. (2001).
[http://dx.doi.org/10.1021/jm010894d] [PMID: 11543689]
[59]
Rampa A, Bisi A, Valenti P, Recanatini M, Cavalli A, Andrisano V, et al. Acetylcholinesterase inhibitors: synthesis and structure-activity relationships of omega-[N-methyl-N-(3-alkylcarbamoyloxyphenyl)- methyl]aminoalkoxyheteroaryl derivatives. J Med Chem 41(21): 3976-86. (1998).
[http://dx.doi.org/10.1021/jm9810046] [PMID: 9767635]
[60]
Snape MF, Misra A, Murray TK, De Souza RJ, Williams JL, Cross AJ, et al. A comparative study in rats of the in vitro and in vivo pharmacology of the acetylcholinesterase inhibitors tacrine, donepezil and NXX-066. Neuropharmacology 38(1): 181-93. (1999).
[http://dx.doi.org/10.1016/S0028-3908(98)00164-6] [PMID: 10193909]
[61]
Bartolini M, Bertucci C, Cavrini V, Andrisano V. beta-Amyloid aggregation induced by human acetylcholinesterase: inhibition studies. Biochem Pharmacol 65(3): 407-16. (2003).
[http://dx.doi.org/10.1016/S0006-2952(02)01514-9] [PMID: 12527333]
[62]
Rizzo S, Bartolini M, Ceccarini L, Piazzi L, Gobbi S, Cavalli A, et al. Targeting Alzheimer’s disease: Novel indanone hybrids bearing a pharmacophoric fragment of AP2238. Bioorg Med Chem 18(5): 1749-60. (2010).
[http://dx.doi.org/10.1016/j.bmc.2010.01.071] [PMID: 20171894]
[63]
Belluti F, Piazzi L, Bisi A, Gobbi S, Bartolini M, Cavalli A, et al. Design, synthesis, and evaluation of benzophenone derivatives as novel acetylcholinesterase inhibitors. Eur J Med Chem 44(3): 1341-8. (2009).
[http://dx.doi.org/10.1016/j.ejmech.2008.02.035] [PMID: 18396354]
[64]
Chen J-J, Ting C-W, Hwang T-L, Chen I-S. Benzophenone derivatives from the fruits of Garcinia multiflora and their anti-inflammatory activity. J Nat Prod 72(2): 253-8. (2009).
[http://dx.doi.org/10.1021/np8006364] [PMID: 19203247]
[65]
Chiang Y-M, Kuo Y-H, Oota S, Fukuyama Y. Xanthones and benzophenones from the stems of Garcinia multiflora. J Nat Prod 66(8): 1070-3. (2003).
[http://dx.doi.org/10.1021/np030065q] [PMID: 12932126]
[66]
Ito C, Itoigawa M, Miyamoto Y, Onoda S, Rao KS, Mukainaka T, et al. Polyprenylated benzophenones from Garcinia assigu and their potential cancer chemopreventive activities. J Nat Prod 66(2): 206-9. (2003).
[http://dx.doi.org/10.1021/np020372g] [PMID: 12608850]
[67]
Belluti F, Bartolini M, Bottegoni G, Bisi A, Cavalli A, Andrisano V, et al. Benzophenone-based derivatives: a novel series of potent and selective dual inhibitors of acetylcholinesterase and acetylcholinesterase-induced beta-amyloid aggregation. Eur J Med Chem 46(5): 1682-93. (2011).
[http://dx.doi.org/10.1016/j.ejmech.2011.02.019] [PMID: 21397996]
[68]
Więckowska A, Bajda M, Guzior N, Malawska B. Novel alkyl- and arylcarbamate derivatives with N-benzylpiperidine and N-benzylpiperazine moieties as cholinesterases inhibitors. Eur J Med Chem 45(12): 5602-11. (2010).
[http://dx.doi.org/10.1016/j.ejmech.2010.09.010] [PMID: 20926161]
[69]
Bajda M, Więckowska A, Hebda M, Guzior N, Sotriffer CA, Malawska B. Structure-based search for new inhibitors of cholinesterases. Int J Mol Sci 14(3): 5608-32. (2013).
[http://dx.doi.org/10.3390/ijms14035608] [PMID: 23478436]
[70]
Ignasik M, Bajda M, Guzior N, Prinz M, Holzgrabe U, Malawska B. Design, synthesis and evaluation of novel 2-(aminoalkyl)-isoindoline-1,3-dione derivatives as dual-binding site acetylcholinesterase inhibitors. Arch Pharm (Weinheim) 345(7): 509-16. (2012).
[http://dx.doi.org/10.1002/ardp.201100423] [PMID: 22467516]
[71]
Greenblatt HM, Guillou C, Guénard D, Argaman A, Botti S, Badet B, et al. The complex of a bivalent derivative of galanthamine with torpedo acetylcholinesterase displays drastic deformation of the active-site gorge: implications for structure-based drug design. J Am Chem Soc 126(47): 15405-11. (2004).
[http://dx.doi.org/10.1021/ja0466154] [PMID: 15563167]
[72]
Guzior N, Bajda M, Skrok M, Kurpiewska K, Lewiński K, Brus B, et al. Development of multifunctional, heterodimeric isoindoline-1,3-dione derivatives as cholinesterase and β-amyloid aggregation inhibitors with neuroprotective properties. Eur J Med Chem 92: 738-49. (2015).
[http://dx.doi.org/10.1016/j.ejmech.2015.01.027] [PMID: 25621991]
[73]
Arias E, Gallego-Sandín S, Villarroya M, García AG, López MG. Unequal neuroprotection afforded by the acetylcholinesterase inhibitors galantamine, donepezil, and rivastigmine in SH-SY5Y neuroblastoma cells: role of nicotinic receptors. J Pharmacol Exp Ther 315(3): 1346-53. (2005).
[http://dx.doi.org/10.1124/jpet.105.090365] [PMID: 16144975]
[74]
Landau M, Sawaya MR, Faull KF, Laganowsky A, Jiang L, Sievers SA, et al. Towards a pharmacophore for amyloid. PLoS Biol 9(6)e1001080 (2011).
[http://dx.doi.org/10.1371/journal.pbio.1001080] [PMID: 21695112]
[75]
Guzior N, Bajda M, Rakoczy J, Brus B, Gobec S, Malawska B. Isoindoline-1,3-dione derivatives targeting cholinesterases: design, synthesis and biological evaluation of potential anti-Alzheimer’s agents. Bioorg Med Chem 23(7): 1629-37. (2015).
[http://dx.doi.org/10.1016/j.bmc.2015.01.045] [PMID: 25707322]
[76]
Szałaj N, Bajda M, Dudek K, Brus B, Gobec S, Malawska B. Multiple ligands targeting cholinesterases and β-amyloid: synthesis, biological evaluation of heterodimeric compounds with benzylamine pharmacophore. Arch Pharm (Weinheim) 348(8): 556-63. (2015).
[http://dx.doi.org/10.1002/ardp.201500117] [PMID: 26032855]
[77]
Hebda M, Bajda M, Więckowska A, Szałaj N, Pasieka A, Panek D, et al. Synthesis, molecular modelling and biological evaluation of novel heterodimeric, multiple ligands targeting cholinesterases and amyloid beta. Molecules 21(4): 410. (2016).
[http://dx.doi.org/10.3390/molecules21040410] [PMID: 27023510]
[78]
Więckowska A, Więckowski K, Bajda M. Brus B3, Sałat K4, Czerwińska P, et al. Synthesis of new N-benzylpiperidine derivatives as cholinesterase inhibitors with β-amyloid anti-aggregation properties and beneficial effects on memory in vivo. Bioorg Med Chem 23(10): 2445-57. (2015).
[http://dx.doi.org/10.1016/j.bmc.2015.03.051] [PMID: 25868744]
[79]
Özturan Özer E, Tan OU, Ozadali K, Küçükkılınç T, Balkan A, Uçar G. Synthesis, molecular modeling and evaluation of novel N′-2-(4-benzylpiperidin-/piperazin-1-yl)acylhydrazone derivatives as dual inhibitors for cholinesterases and Aβ aggregation. Bioorg Med Chem Lett 23(2): 440-3. (2013).
[http://dx.doi.org/10.1016/j.bmcl.2012.11.064] [PMID: 23273219]
[80]
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 46(1-3): 3-26. (2001).
[http://dx.doi.org/10.1016/S0169-409X(00)00129-0] [PMID: 11259830]
[81]
Benhamú B, Martín-Fontecha M, Vázquez-Villa H, Pardo L, López-Rodríguez ML. Serotonin 5-HT6 receptor antagonists for the treatment of cognitive deficiency in Alzheimer’s disease. J Med Chem 57(17): 7160-81. (2014).
[http://dx.doi.org/10.1021/jm5003952] [PMID: 24850589]
[82]
Foley AG, Hirst WD, Gallagher HC, Barry C, Hagan JJ, Upton N, et al. The selective 5-HT6 receptor antagonists SB-271046 and SB-399885 potentiate NCAM PSA immunolabeling of dentate granule cells, but not neurogenesis, in the hippocampal formation of mature Wistar rats. Neuropharmacology 54(8): 1166-74. (2008).
[http://dx.doi.org/10.1016/j.neuropharm.2008.03.012] [PMID: 18455201]
[83]
Routledge C, Bromidge SM, Moss SF, Price GW, Hirst W, Newman H, et al. Characterization of SB-271046: a potent, selective and orally active 5-HT(6) receptor antagonist. Br J Pharmacol 130(7): 1606-12. (2000).
[http://dx.doi.org/10.1038/sj.bjp.0703457] [PMID: 10928964]
[84]
Więckowska A, Kołaczkowski M, Bucki A, Godyń J, Marcinkowska M, Więckowski K, et al. Novel multi-target-directed ligands for Alzheimer’s disease: combining cholinesterase inhibitors and 5-HT6 receptor antagonists. Design, synthesis and biological evaluation. Eur J Med Chem 124: 63-81. (2016).
[http://dx.doi.org/10.1016/j.ejmech.2016.08.016] [PMID: 27560283]
[85]
Arce MP, Rodríguez-Franco MI, González-Muñoz GC, et al. Neuroprotective and cholinergic properties of multifunctional glutamic acid derivatives for the treatment of Alzheimer’s disease. J Med Chem 52(22): 7249-57. (2009).
[http://dx.doi.org/10.1021/jm900628z] [PMID: 19856923]
[86]
Prokai-Tatrai K, Nguyen V, Zharikova AD, Braddy AC, Stevens SM, Prokai L. Prodrugs to enhance central nervous system effects of the TRH-like peptide pGlu-Glu-Pro-NH2. Bioorg Med Chem Lett 13(6): 1011-4. (2003).
[http://dx.doi.org/10.1016/S0960-894X(03)00081-7] [PMID: 12643900]
[88]
Chakraborty S, Bandyopadhyay J, Chakraborty S, Basu S. Multi-target screening mines hesperidin as a multi-potent inhibitor: implication in Alzheimer’s disease therapeutics. Eur J Med Chem 121: 810-22. (2016).
[http://dx.doi.org/10.1016/j.ejmech.2016.03.057] [PMID: 27068363]
[89]
New Journal of Chemistry (RSC Publishing) https://pubs.rsc.org/en/content/articlehtml/2018/nj/c8nj00853a [10.1039/C8NJ00853A];
[90]
Belluti F, Rampa A, Piazzi L, Bisi A, Gobbi S, Bartolini M, et al. Cholinesterase inhibitors: xanthostigmine derivatives blocking the acetylcholinesterase-induced beta-amyloid aggregation. J Med Chem 48(13): 4444-56. (2005).
[http://dx.doi.org/10.1021/jm049515h] [PMID: 15974596]
[91]
Piazzi L, Cavalli A, Belluti F, et al. Extensive SAR and computational studies of 3-4-[(benzylmethylamino)methyl]phenyl-6,7-dimethoxy-2H-2-chromenone (AP2238) derivatives. J Med Chem 50(17): 4250-4. (2007).
[http://dx.doi.org/10.1021/jm070100g] [PMID: 17655212]
[92]
Rampa A, Piazzi L, Belluti F, Gobbi S, Bisi A, Bartolini M, et al. Acetylcholinesterase inhibitors: SAR and kinetic studies on omega-[N-methyl-N-(3-alkylcarbamoyloxyphenyl)methyl]aminoalkoxyaryl derivatives. J Med Chem 44(23): 3810-20. (2001).
[http://dx.doi.org/10.1021/jm010914b] [PMID: 11689067]
[93]
Rizzo S, Cavalli A, Ceccarini L, Bartolini M, Belluti F, Bisi A, et al. Structure-activity relationships and binding mode in the human acetylcholinesterase active site of pseudo-irreversible inhibitors related to xanthostigmine. ChemMedChem 4(4): 670-9. (2009).
[http://dx.doi.org/10.1002/cmdc.200800396] [PMID: 19222043]
[94]
Piazzi L, Belluti F, Bisi A, Gobbi S, Rizzo S, Bartolini M, et al. Cholinesterase inhibitors: SAR and enzyme inhibitory activity of 3-[omega-(benzylmethylamino)alkoxy]xanthen-9-ones. Bioorg Med Chem 15(1): 575-85. (2007).
[http://dx.doi.org/10.1016/j.bmc.2006.09.026] [PMID: 17008100]
[95]
Sugimoto H, Yamanishi Y, Iimura Y, Kawakami Y. Donepezil hydrochloride (E2020) and other acetylcholinesterase inhibitors. Curr Med Chem 7(3): 303-39. (2000).
[http://dx.doi.org/10.2174/0929867003375191] [PMID: 10637367]
[96]
Perola E, Cellai L, Lamba D, Filocamo L, Brufani M. Long chain analogs of physostigmine as potential drugs for Alzheimer’s disease: new insights into the mechanism of action in the inhibition of acetylcholinesterase. Biochim Biophys Acta 1343(1): 41-50. (1997).
[http://dx.doi.org/10.1016/S0167-4838(97)00133-7] [PMID: 9428657]
[97]
Bag S, Tulsan R, Sood A, Cho H, Redjeb H, Zhou W, et al. Sulfonamides as multifunctional agents for Alzheimer’s disease. Bioorg Med Chem Lett 25(3): 626-30. (2015).
[http://dx.doi.org/10.1016/j.bmcl.2014.12.006] [PMID: 25537270]
[98]
Sood A, Abid M, Sauer C, Hailemichael S, Foster M, Török B, et al. Disassembly of preformed amyloid beta fibrils by small organofluorine molecules. Bioorg Med Chem Lett 21(7): 2044-7. (2011).
[http://dx.doi.org/10.1016/j.bmcl.2011.02.012] [PMID: 21354796]
[99]
Borkin D, Morzhina E, Datta S, Rudnitskaya A, Sood A, Török M, et al. Heteropoly acid-catalyzed microwave-assisted three-component aza-Diels-Alder cyclizations: diastereoselective synthesis of potential drug candidates for Alzheimer’s disease. Org Biomol Chem 9(5): 1394-401. (2011).
[http://dx.doi.org/10.1039/c0ob00638f] [PMID: 21210035]
[100]
Török B, Sood A, Bag S, Tulsan R, Ghosh S, Borkin D, et al. Diaryl hydrazones as multifunctional inhibitors of amyloid self-assembly. Biochemistry 52(7): 1137-48. (2013).
[http://dx.doi.org/10.1021/bi3012059] [PMID: 23346953]
[101]
Bag S, Ghosh S, Tulsan R, Sood A, Zhou W, Schifone C, et al. Design, synthesis and biological activity of multifunctional α,β-unsaturated carbonyl scaffolds for Alzheimer’s disease. Bioorg Med Chem Lett 23(9): 2614-8. (2013).
[http://dx.doi.org/10.1016/j.bmcl.2013.02.103] [PMID: 23540646]
[102]
Cai P, Fang S-Q, Yang X-L, Wu JJ, Liu QH, Hong H, et al. Rational design and multibiological profiling of novel donepezil–trolox hybrids against alzheimer’s disease, with cholinergic, antioxidant, neuroprotective, and cognition enhancing properties. ACS Chem Neurosci 8(11): 2496-511. (2017).
[http://dx.doi.org/10.1021/acschemneuro.7b00257] [PMID: 28806057]
[103]
Riederer P, Danielczyk W, Grünblatt E. Monoamine oxidase-B inhibition in Alzheimer’s disease. Neurotoxicology 25(1-2): 271-7. (2004).
[http://dx.doi.org/10.1016/S0161-813X(03)00106-2] [PMID: 14697902]
[104]
De Ferrari GV, Canales MA, Shin I, Weiner LM, Silman I, Inestrosa NC. A structural motif of acetylcholinesterase that promotes amyloid beta-peptide fibril formation. Biochemistry 40(35): 10447-57. (2001).
[http://dx.doi.org/10.1021/bi0101392] [PMID: 11523986]
[105]
Alipour M, Khoobi M, Moradi A, Nadri H, Homayouni Moghadam F, Emami S, et al. Synthesis and anti-cholinesterase activity of new 7-hydroxycoumarin derivatives. Eur J Med Chem 82: 536-44. (2014).
[http://dx.doi.org/10.1016/j.ejmech.2014.05.056] [PMID: 24941128]
[106]
Kontogiorgis CA, Xu Y, Hadjipavlou-Litina D, Luo Y. Coumarin derivatives protection against ROS production in cellular models of Abeta toxicities. Free Radic Res 41(10): 1168-80. (2007).
[http://dx.doi.org/10.1080/10715760701447884] [PMID: 17886039]
[107]
Prasad S, Kumar B, Kumar S, Chand K, Kamble SS, Gautam HK, et al. Acetamide derivatives of chromen-2-ones as potent cholinesterase inhibitors. Arch Pharm (Weinheim) 350(8)1700076 (2017).
[http://dx.doi.org/10.1002/ardp.201700076] [PMID: 28699213]
[108]
Mohamed LW, Abuel-Maaty SM, Mohammed WA, Galal MA. Synthesis and biological evaluation of new oxopyrrolidine derivatives as inhibitors of acetyl cholinesterase and β amyloid protein as anti - Alzheimer’s agents. Bioorg Chem 76: 210-7. (2018).
[http://dx.doi.org/10.1016/j.bioorg.2017.11.008] [PMID: 29190477]
[109]
Washington PM, Morffy N, Parsadanian M, Zapple DN, Burns MP. Experimental traumatic brain injury induces rapid aggregation and oligomerization of amyloid-beta in an Alzheimer’s disease mouse model. J Neurotrauma 31(1): 125-34. (2014).
[http://dx.doi.org/10.1089/neu.2013.3017] [PMID: 24050316]
[110]
Hiremathad A, Chand K, Tolayan L. Rajeshwari, Keri RS, Esteves AR, et al. Hydroxypyridinone-benzofuran hybrids with potential protective roles for Alzheimer’s disease therapy. J Inorg Biochem 179: 82-96. (2018).
[http://dx.doi.org/10.1016/j.jinorgbio.2017.11.015] [PMID: 29182921]
[111]
Bolea I, Juárez-Jiménez J, de Los Ríos C, Chioua M, Pouplana R, Luque FJ, et al. Synthesis, biological evaluation, and molecular modeling of donepezil and N-[(5-(benzyloxy)-1-methyl-1H-indol-2-yl)methyl]-N-methylprop-2-yn-1-amine hybrids as new multipotent cholinesterase/monoamine oxidase inhibitors for the treatment of Alzheimer’s disease. J Med Chem 54(24): 8251-70. (2011).
[http://dx.doi.org/10.1021/jm200853t] [PMID: 22023459]
[112]
Cole SL, Vassar R. BACE1 structure and function in health and Alzheimer’s disease. Curr Alzheimer Res 5(2): 100-20. (2008).
[http://dx.doi.org/10.2174/156720508783954758] [PMID: 18393796]
[113]
Yan R, Bienkowski MJ, Shuck ME, Miao H, Tory MC, Pauley AM, et al. Membrane-anchored aspartyl protease with Alzheimer’s disease beta-secretase activity. Nature 402(6761): 533-7. (1999).
[http://dx.doi.org/10.1038/990107] [PMID: 10591213]
[114]
Huse JT, Liu K, Pijak DS, Carlin D, Lee VM-Y, Doms RW. Beta-secretase processing in the trans-Golgi network preferentially generates truncated amyloid species that accumulate in Alzheimer’s disease brain. J Biol Chem 277(18): 16278-84. (2002).
[http://dx.doi.org/10.1074/jbc.M111141200] [PMID: 11847218]
[115]
Fleck D, Garratt AN, Haass C, Willem M. BACE1 dependent neuregulin processing. review Curr Alzheimer Res 9(2): 178-83. (2012). [review].
[http://dx.doi.org/10.2174/156720512799361637] [PMID: 22455478]
[116]
Tamagno E, Guglielmotto M, Monteleone D, Tabaton M. Amyloid-β production: major link between oxidative stress and BACE1. Neurotox Res 22(3): 208-19. (2012).
[http://dx.doi.org/10.1007/s12640-011-9283-6] [PMID: 22002808]
[117]
Velliquette RA, O’Connor T, Vassar R. Energy inhibition elevates beta-secretase levels and activity and is potentially amyloidogenic in APP transgenic mice: possible early events in Alzheimer’s disease pathogenesis. J Neurosci 25(47): 10874-83. (2005).
[http://dx.doi.org/10.1523/JNEUROSCI.2350-05.2005] [PMID: 16306400]
[118]
Ohno M, Chang L, Tseng W, Oakley H, Citron M, Klein WL, et al. Temporal memory deficits in Alzheimer’s mouse models: rescue by genetic deletion of BACE1. Eur J Neurosci 23(1): 251-60. (2006).
[http://dx.doi.org/10.1111/j.1460-9568.2005.04551.x] [PMID: 16420434]
[119]
Roberds SL, Anderson J, Basi G, Bienkowski MJ, Branstetter DG, Chen KS, et al. BACE knockout mice are healthy despite lacking the primary beta-secretase activity in brain: implications for Alzheimer’s disease therapeutics. Hum Mol Genet 10(12): 1317-24. (2001).
[http://dx.doi.org/10.1093/hmg/10.12.1317] [PMID: 11406613]
[120]
Stachel SJ, Coburn CA, Steele TG, Jones KG, Loutzenhiser EF, Gregro AR, et al. Structure-based design of potent and selective cell-permeable inhibitors of human beta-secretase (BACE-1). J Med Chem 47(26): 6447-50. (2004).
[http://dx.doi.org/10.1021/jm049379g] [PMID: 15588077]
[121]
Zhu Y, Xiao K, Ma L, Xiong B, Fu Y, Yu H, et al. Design, synthesis and biological evaluation of novel dual inhibitors of acetylcholinesterase and beta-secretase. Bioorg Med Chem 17(4): 1600-13. (2009).
[http://dx.doi.org/10.1016/j.bmc.2008.12.067] [PMID: 19162488]
[122]
Rampa A, Mancini F, De Simone A, Falchi F, Belluti F, Di Martino RM, et al. From AChE to BACE1 inhibitors: The role of the amine on the indanone scaffold. Bioorg Med Chem Lett 25(14): 2804-8. (2015).
[http://dx.doi.org/10.1016/j.bmcl.2015.05.002] [PMID: 26003339]
[123]
Costanzo P, Cariati L, Desiderio D, Sgammato R, Lamberti A, Arcone R, et al. Design, synthesis, and evaluation of donepezil-like compounds as AChE and BACE-1 inhibitors. ACS Med Chem Lett 7(5): 470-5. (2016).
[http://dx.doi.org/10.1021/acsmedchemlett.5b00483] [PMID: 27190595]
[124]
Viayna E, Gómez T, Galdeano C, Ramírez L, Ratia M, Badia A, et al. Novel huprine derivatives with inhibitory activity toward β-amyloid aggregation and formation as disease-modifying anti-Alzheimer drug candidates. ChemMedChem 5(11): 1855-70. (2010).
[http://dx.doi.org/10.1002/cmdc.201000322] [PMID: 20859987]
[125]
Muñoz-Torrero D, Camps P. Dimeric and hybrid anti-Alzheimer drug candidates. Curr Med Chem 13(4): 399-422. (2006).
[http://dx.doi.org/10.2174/092986706775527974] [PMID: 16475930]
[126]
Canudas AM, Pubill D, Sureda FX, Verdaguer E, Camps P, Muñoz-Torrero D, et al. Neuroprotective effects of (+/-)-huprine Y on in vitro and in vivo models of excitoxicity damage. Exp Neurol 180(2): 123-30. (2003).
[http://dx.doi.org/10.1016/S0014-4886(02)00029-8] [PMID: 12684026]
[127]
Muñoz-Torrero D, Camps P. Huprines for Alzheimer’s disease drug development. Expert Opin Drug Discov 3(1): 65-81. (2008).
[http://dx.doi.org/10.1517/17460441.3.1.65] [PMID: 23480140]
[128]
Ratia M, Giménez-Llort L, Camps P, Muñoz-Torrero D, Clos MV, Badia A. Behavioural effects and regulation of PKCalpha and MAPK by huprine X in middle aged mice. Pharmacol Biochem Behav 95(4): 485-93. (2010).
[http://dx.doi.org/10.1016/j.pbb.2010.03.013] [PMID: 20363245]
[129]
Dvir H, Wong DM, Harel M, Barril X, Orozco M, Luque FJ, et al. 3D structure of Torpedo californica acetylcholinesterase complexed with huprine X at 2.1 A resolution: kinetic and molecular dynamic correlates. Biochemistry 41(9): 2970-81. (2002).
[http://dx.doi.org/10.1021/bi011652i] [PMID: 11863435]
[130]
Camps P, Contreras J, Font-Bardia M, Morral J, Muñoz-Torrero D, Solans X. Enantioselective synthesis of tacrine–huperzine A hybrids. Preparative chiral MPLC separation of their racemic mixtures and absolute configuration assignments by X-ray diffraction analysis. Tetrahedron Asymmetry 9(5): 835-49. (1998).
[http://dx.doi.org/10.1016/S0957-4166(98)00029-9]
[131]
Camps P, Cusack B, Mallender WD, El Achab RE, Morral J, Muñoz-Torrero D, et al. Huprine X is a novel high-affinity inhibitor of acetylcholinesterase that is of interest for treatment of Alzheimer’s disease. Mol Pharmacol 57(2): 409-17. (2000).
[PMID: 10648652]
[132]
Camps P, Morral J, Muñoz-Torrero D, Muñoz-Torrero D, Badia A, Baños JE, et al. New tacrine-huperzine A hybrids (huprines): highly potent tight-binding acetylcholinesterase inhibitors of interest for the treatment of Alzheimer’s disease. J Med Chem 43(24): 4657-66. (2000).
[http://dx.doi.org/10.1021/jm000980y] [PMID: 11101357]
[133]
Recanatini M, Cavalli A, Belluti F, Piazzi L, Rampa A, Bisi A, et al. SAR of 9-amino-1,2,3,4-tetrahydroacridine-based acetylcholinesterase inhibitors: synthesis, enzyme inhibitory activity, QSAR, and structure-based CoMFA of tacrine analogues. J Med Chem 43(10): 2007-18. (2000).
[http://dx.doi.org/10.1021/jm990971t] [PMID: 10821713]
[134]
De Strooper B, Vassar R, Golde T. The secretases: enzymes with therapeutic potential in Alzheimer disease. Nat Rev Neurol 6(2): 99-107. (2010).
[http://dx.doi.org/10.1038/nrneurol.2009.218] [PMID: 20139999]
[135]
Tumiatti V, Rosini M, Bartolini M, Cavalli A, Marucci G, Andrisano V, et al. Structure-activity relationships of acetylcholinesterase noncovalent inhibitors based on a polyamine backbone. 2. Role of the substituents on the phenyl ring and nitrogen atoms of caproctamine. J Med Chem 46(6): 954-66. (2003).
[http://dx.doi.org/10.1021/jm021055+] [PMID: 12620072]
[136]
Tarozzi A, Bartolini M, Piazzi L, Valgimigli L, Amorati R, Bolondi C, et al. From the dual function lead AP2238 to AP2469, a multi-target-directed ligand for the treatment of Alzheimer’s disease. Pharmacol Res Perspect 2(2)e00023 (2014).
[http://dx.doi.org/10.1002/prp2.23] [PMID: 25505579]
[137]
Huong VT, Shimanouchi T, Shimauchi N, Yagi H, Umakoshi H, Goto Y, et al. Catechol derivatives inhibit the fibril formation of amyloid-beta peptides. J Biosci Bioeng 109(6): 629-34. (2010).
[http://dx.doi.org/10.1016/j.jbiosc.2009.11.010] [PMID: 20471605]
[138]
Amorati R, Valgimigli L. Modulation of the antioxidant activity of phenols by non-covalent interactions. Org Biomol Chem 10(21): 4147-58. (2012).
[http://dx.doi.org/10.1039/c2ob25174d] [PMID: 22505046]
[139]
Shimmyo Y, Kihara T, Akaike A, Niidome T, Sugimoto H. Flavonols and flavones as BACE-1 inhibitors: structure-activity relationship in cell-free, cell-based and in silico studies reveal novel pharmacophore features. Biochim Biophys Acta 1780(5): 819-25. (2008).
[http://dx.doi.org/10.1016/j.bbagen.2008.01.017] [PMID: 18295609]
[140]
Clementi ME, Marini S, Coletta M, Orsini F, Giardina B, Misiti F. Abeta(31-35) and Abeta(25-35) fragments of amyloid beta-protein induce cellular death through apoptotic signals: role of the redox state of methionine-35. FEBS Lett 579(13): 2913-8. (2005).
[http://dx.doi.org/10.1016/j.febslet.2005.04.041] [PMID: 15890345]
[141]
Mohamed T, Yeung JCK, Rao PPN. Development of 2-substituted-N-(naphth-1-ylmethyl) and N-benzhydrylpyrimidin-4-amines as dual cholinesterase and Aβ-aggregation inhibitors: Synthesis and biological evaluation. Bioorg Med Chem Lett 21(19): 5881-7. (2011).
[http://dx.doi.org/10.1016/j.bmcl.2011.07.091] [PMID: 21873056]
[142]
Mohamed T, Zhao X, Habib LK, Yang J, Rao PPN. Design, synthesis and structure-activity relationship (SAR) studies of 2,4-disubstituted pyrimidine derivatives: dual activity as cholinesterase and Aβ-aggregation inhibitors. Bioorg Med Chem 19(7): 2269-81. (2011).
[http://dx.doi.org/10.1016/j.bmc.2011.02.030] [PMID: 21429752]
[143]
Mohamed T, Rao PPN. Design, synthesis and evaluation of 2,4-disubstituted pyrimidines as cholinesterase inhibitors. Bioorg Med Chem Lett 20(12): 3606-9. (2010).
[http://dx.doi.org/10.1016/j.bmcl.2010.04.108] [PMID: 20472431]
[144]
Mohamed T, Yeung JCK, Vasefi MS, Beazely MA, Rao PPN. Development and evaluation of multifunctional agents for potential treatment of Alzheimer’s disease: application to a pyrimidine-2,4-diamine template. Bioorg Med Chem Lett 22(14): 4707-12. (2012).
[http://dx.doi.org/10.1016/j.bmcl.2012.05.077] [PMID: 22704921]
[145]
Steele TG, Hills ID, Nomland AA, de León P, Allison T, McGaughey G, et al. Identification of a small molecule beta-secretase inhibitor that binds without catalytic aspartate engagement. Bioorg Med Chem Lett 19(1): 17-20. (2009).
[http://dx.doi.org/10.1016/j.bmcl.2008.11.027] [PMID: 19036583]
[146]
López-Iglesias B, Pérez C, Morales-García JA, Alonso-Gil S, Pérez-Castillo A, Romero A, et al. New melatonin-N,N-dibenzyl(N-methyl)amine hybrids: potent neurogenic agents with antioxidant, cholinergic, and neuroprotective properties as innovative drugs for Alzheimer’s disease. J Med Chem 57(9): 3773-85. (2014).
[http://dx.doi.org/10.1021/jm5000613] [PMID: 24738476]
[147]
Fernández-Bachiller MI, Pérez C, Campillo NE, Páez JA, González-Muñoz GC, Usán P, et al. Tacrine-melatonin hybrids as multifunctional agents for Alzheimer’s disease, with cholinergic, antioxidant, and neuroprotective properties. ChemMedChem 4(5): 828-41. (2009).
[http://dx.doi.org/10.1002/cmdc.200800414] [PMID: 19308922]
[148]
Hardeland R. Melatonin and the theories of aging: a critical appraisal of melatonin’s role in antiaging mechanisms. J Pineal Res 55(4): 325-56. (2013).
[http://dx.doi.org/10.1111/jpi.12090] [PMID: 24112071]
[149]
Benek O, Musilek K, Horova A, Dohnal V, Dolezal R, Kuca K. Preparation, in vitro screening and molecular modelling of monoquaternary compounds related to the selective acetylcholinesterase inhibitor BW284c51. Med Chem 11(1): 21-9. (2014).
[http://dx.doi.org/10.2174/1573406410666140428153110] [PMID: 24773345]
[150]
Kwon YE, Park JY, No KT, Shin JH, Lee SK, Eun JS, et al. Synthesis, in vitro assay, and molecular modeling of new piperidine derivatives having dual inhibitory potency against acetylcholinesterase and Abeta1-42 aggregation for Alzheimer’s disease therapeutics. Bioorg Med Chem 15(20): 6596-607. (2007).
[http://dx.doi.org/10.1016/j.bmc.2007.07.003] [PMID: 17681794]
[151]
Panek D, Więckowska A, Wichur T, Bajda M, Godyń J, Jończyk J, et al. Design, synthesis and biological evaluation of new phthalimide and saccharin derivatives with alicyclic amines targeting cholinesterases, beta-secretase and amyloid beta aggregation. Eur J Med Chem 125: 676-95. (2017).
[http://dx.doi.org/10.1016/j.ejmech.2016.09.078] [PMID: 27721153]
[152]
Laras Y, Garino C, Dessolin J, Weck C, Moret V, Rolland A, et al. New N(4)-substituted piperazine naphthamide derivatives as BACE-1 inhibitors. J Enzyme Inhib Med Chem 24(1): 181-7. (2009).
[http://dx.doi.org/10.1080/14756360802048939] [PMID: 18770069]
[153]
Ghosh AK, Osswald HL. BACE1 (β-secretase) inhibitors for the treatment of Alzheimer’s disease. Chem Soc Rev 43(19): 6765-813. (2014).
[http://dx.doi.org/10.1039/C3CS60460H] [PMID: 24691405]
[154]
Panek D, Więckowska A, Jończyk J, Godyń J, Bajda M, Wichur T, et al. Design, synthesis, and biological evaluation of 1-benzylamino-2-hydroxyalkyl derivatives as new potential disease-modifying multifunctional anti-alzheimer’s agents. ACS Chem Neurosci 9(5): 1074-94. (2018).
[http://dx.doi.org/10.1021/acschemneuro.7b00461] [PMID: 29345897]
[155]
Panek D, Więckowska A, Pasieka A, Godyń J, Jończyk J, Bajda M, et al. Design, synthesis, and biological evaluation of 2-(Benzylamino-2-Hydroxyalkyl)Isoindoline-1,3-diones derivatives as potential disease-modifying multifunctional anti-alzheimer agents. Molecules 23(2): 347. (2018).
[http://dx.doi.org/10.3390/molecules23020347] [PMID: 29414887]
[156]
Chalupova K, Korabecny J, Bartolini M, Monti B, Lamba D, Caliandro R, et al. Novel tacrine-tryptophan hybrids: Multi-target directed ligands as potential treatment for Alzheimer’s disease. Eur J Med Chem 168: 491-514. (2019).
[157]
Dias Viegas FP, de Freitas Silva M, Divino da Rocha M, Castelli MR, Riquiel MM, Machado RP, et al. Design, synthesis and pharmacological evaluation of N-benzyl-piperidinyl-aryl-acylhydrazone derivatives as donepezil hybrids: discovery of novel multi-target anti-alzheimer prototype drug candidates. Eur J Med Chem 147: 48-65. (2018).
[http://dx.doi.org/10.1016/j.ejmech.2018.01.066] [PMID: 29421570]
[158]
da Silva YKC, Augusto CV, de Castro Barbosa ML, de Albuquerque Melo GM, de Queiroz AC, de Lima Matos Freire Dias T, et al. Synthesis and pharmacological evaluation of pyrazine N-acylhydrazone derivatives designed as novel analgesic and anti-inflammatory drug candidates. Bioorg Med Chem 18(14): 5007-15. (2010).
[http://dx.doi.org/10.1016/j.bmc.2010.06.002] [PMID: 20598893]
[159]
Lemes LFN, de Andrade Ramos G, de Oliveira AS, da Silva FMR, de Castro Couto G, da Silva Boni M, et al. Cardanol-derived AChE inhibitors: Towards the development of dual binding derivatives for Alzheimer’s disease. Eur J Med Chem 108: 687-700. (2016).
[http://dx.doi.org/10.1016/j.ejmech.2015.12.024] [PMID: 26735910]
[160]
Palanimuthu D, Poon R, Sahni S, Anjum R, Hibbs D, Lin HY, et al. A novel class of thiosemicarbazones show multi-functional activity for the treatment of Alzheimer’s disease. Eur J Med Chem 139: 612-32. (2017).
[http://dx.doi.org/10.1016/j.ejmech.2017.08.021] [PMID: 28841514]
[161]
Li L, Xu S, Liu L, Gong Y, Zhao X, Li J, et al. Multifunctional compound ad-35 improves cognitive impairment and attenuates the production of tnf-α and il-1β in an aβ25-35-induced rat model of Alzheimer’s disease. J Alzheimers Dis 56(4): 1403-17. (2017).
[http://dx.doi.org/10.3233/JAD-160587] [PMID: 28157092]
[162]
Sonkusare SK, Kaul CL, Ramarao P. Dementia of Alzheimer’s disease and other neurodegenerative disorders--memantine, a new hope. Pharmacol Res 51(1): 1-17. (2005).
[http://dx.doi.org/10.1016/j.phrs.2004.05.005] [PMID: 15519530]
[163]
Spilovska K, Zemek F, Korabecny J, Nepovimova E, Soukup O, Windisch M, et al. Adamantane - a lead structure for drugs in clinical practice. Curr Med Chem 23(29): 3245-66. (2016).
[http://dx.doi.org/10.2174/0929867323666160525114026] [PMID: 27222266]
[164]
Coric V, Salloway S, van Dyck CH. Dubois B4, Andreasen N5, Brody M, et al. Targeting prodromal alzheimer disease with avagacestat: a randomized clinical trial. JAMA Neurol 72(11): 1324-33. (2015).
[http://dx.doi.org/10.1001/jamaneurol.2015.0607] [PMID: 26414022]
[165]
Honig LS, Vellas B, Woodward M. Boada M1, Bullock R1, Borrie M, et al. Trial of solanezumab for mild dementia due to Alzheimer’s disease. N Engl J Med 378(4): 321-30. (2018).
[http://dx.doi.org/10.1056/NEJMoa1705971] [PMID: 29365294]
[166]
Morphy R, Rankovic Z. Multitarget drugs: strategies and challenges for medicinal chemists The Practice of Medicinal Chemistry 4th ed. 2008; pp. 449-72.
[http://dx.doi.org/10.1016/B978-0-12-417205-0.00019-5]

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