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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

Recent Studies on Design and Development of Drugs Against Alzheimer’s Disease (AD) Based on Inhibition of BACE-1 and Other AD-causative Agents

Author(s): Satya P. Gupta* and Vaishali M. Patil

Volume 20, Issue 13, 2020

Page: [1195 - 1213] Pages: 19

DOI: 10.2174/1568026620666200416091623

Price: $65

Abstract

Background: Alzheimer’s disease (AD) is one of the neurodegenerative diseases and has been hypothesized to be a protein misfolding disease. In the generation of AD, β-secretase, γ-secretase, and tau protein play an important role. A literature search reflects ever increasing interest in the design and development of anti-AD drugs targeting β-secretase, γ-secretase, and tau protein.

Objective: The objective is to explore the structural aspects and role of β-secretase, γ-secretase, and tau protein in AD and the efforts made to exploit them for the design of effective anti-AD drugs.

Methods: The manuscript covers the recent studies on design and development of anti-AD drugs exploiting amyloid and cholinergic hypotheses.

Results: Based on amyloid and cholinergic hypotheses, effective anti-AD drugs have been searched out in which non-peptidic BACE1 inhibitors have been most prominent.

Conclusion: Further exploitation of the structural aspects and the inhibition mechanism for β-secretase, γ-secretase, and tau protein and the use of cholinergic hypothesis may lead still more potent anti-AD drugs.

Keywords: Alzheimer's disease, β-secretase, BACE1, γ-secretase, Amyloid precursor protein, tau protein, Anti-AD drugs.

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[1]
Whitehouse, P.J.; Price, D.L.; Struble, R.G.; Clark, A.W.; Coyle, J.T.; Delon, M.R. Alzheimer’s disease and senile dementia: loss of neurons in the basal forebrain. Science, 1982, 215(4537), 1237-1239.
[http://dx.doi.org/10.1126/science.7058341] [PMID: 7058341]
[2]
Sabat, S.R.; Collins, M. Intact social, cognitive ability, and selfhood: A case study of Alzheimer’s disease. Am. J. Alzheimers Dis. (Columbia), 1999, 4, 11-19.
[http://dx.doi.org/10.1177/153331759901400108]
[3]
Pettenati, C.; Annicchiarico, R.; Caltagirone, C. Clinical pharmacology of anti-Alzheimer drugs. Fundam. Clin. Pharmacol., 2003, 17(6), 659-672.
[http://dx.doi.org/10.1046/j.1472-8206.2003.00204.x] [PMID: 15015711]
[4]
Mortby, M.E.; Black, S.E.; Gauthier, S.; Miller, D.; Porsteinsson, A.; Smith, E.E.; Ismail, Z. Dementia clinical trial implications of mild behavioral impairment. Int. Psychogeriatr., 2018, 30(2), 171-175.
[http://dx.doi.org/10.1017/S1041610218000042] [PMID: 29448970]
[5]
Hashimoto, M.; Rockenstein, E.; Crews, L.; Masliah, E. Role of protein aggregation in mitochondrial dysfunction and neurodegeneration in Alzheimer’s and Parkinson’s diseases. Neuromolecular Med., 2003, 4(1-2), 21-36.
[http://dx.doi.org/10.1385/NMM:4:1-2:21] [PMID: 14528050]
[6]
Priller, C.; Bauer, T.; Mitteregger, G.; Krebs, B.; Kretzschmar, H.A.; Herms, J. Synapse formation and function is modulated by the amyloid precursor protein. J. Neurosci., 2006, 26(27), 7212-7221.
[http://dx.doi.org/10.1523/JNEUROSCI.1450-06.2006] [PMID: 16822978]
[7]
Turner, P.R.; O’Connor, K.; Tate, W.P.; Abraham, W.C. Roles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory. Prog. Neurobiol., 2003, 70(1), 1-32.
[http://dx.doi.org/10.1016/S0301-0082(03)00089-3] [PMID: 12927332]
[8]
Hooper, N.M. Roles of proteolysis and lipid rafts in the processing of the amyloid precursor protein and prion protein. Biochem. Soc. Trans., 2005, 33(Pt 2), 335-338.
[http://dx.doi.org/10.1042/BST0330335] [PMID: 15787600]
[9]
Tiraboschi, P.; Hansen, L.A.; Thal, L.J.; Corey-Bloom, J. The importance of neuritic plaques and tangles to the development and evolution of AD. Neurology, 2004, 62(11), 1984-1989.
[http://dx.doi.org/10.1212/01.WNL.0000129697.01779.0A] [PMID: 15184601]
[10]
Maia, M.A.; Sousa, E. BACE-1 and gamma-secretase as therapeutic targets for Alzheimer’s disease. Pharmaceuticals (Basel), 2019, 12(1), 41.
[http://dx.doi.org/10.3390/ph12010041] [PMID: 30893882]
[11]
Citron, M. Alzheimer’s disease: strategies for disease modification. Nat. Rev. Drug Discov., 2010, 9(5), 387-398.
[http://dx.doi.org/10.1038/nrd2896] [PMID: 20431570]
[12]
Yan, R.; Bienkowski, M.J.; Shuck, M.E.; Miao, H.; Tory, M.C.; Pauley, A.M.; Brashier, J.R.; Stratman, N.C.; Mathews, W.R.; Buhl, A.E.; Carter, D.B.; Tomasselli, A.G.; Parodi, L.A.; Heinrikson, R.L.; Gurney, M.E. Membrane-anchored aspartyl protease with Alzheimer’s disease β-secretase activity. Nature, 1999, 402(6761), 533-537.
[http://dx.doi.org/10.1038/990107] [PMID: 10591213]
[13]
Bero, A.W.; Yan, P.; Roh, J.H.; Cirrito, J.R.; Stewart, F.R.; Raichle, M.E.; Lee, J.M.; Holtzman, D.M. Neuronal activity regulates the regional vulnerability to amyloid-β deposition. Nat. Neurosci., 2011, 14(6), 750-756.
[http://dx.doi.org/10.1038/nn.2801] [PMID: 21532579]
[14]
Rovelet-Lecrux, A.; Hannequin, D.; Raux, G.; Le Meur, N.; Laquerrière, A.; Vital, A.; Dumanchin, C.; Feuillette, S.; Brice, A.; Vercelletto, M.; Dubas, F.; Frebourg, T.; Campion, D. APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy. Nat. Genet., 2006, 38(1), 24-26.
[http://dx.doi.org/10.1038/ng1718] [PMID: 16369530]
[15]
Ghosh, A.K.; Osswald, H.L. BACE1 (β-secretase) inhibitors for the treatment of Alzheimer’s disease. Chem. Soc. Rev., 2014, 43(19), 6765-6813.
[http://dx.doi.org/10.1039/C3CS60460H] [PMID: 24691405]
[16]
Hong, L.; Koelsch, G.; Lin, X.; Wu, S.; Terzyan, S.; Ghosh, A.K.; Zhang, X.C.; Tang, J. Structure of the protease domain of memapsin 2 (β-secretase) complexed with inhibitor. Science, 2000, 290, 150-153.
[http://dx.doi.org/10.1126/science.290.5489.150] [PMID: 11021803]
[17]
(a) Hong, L.; Turner, R.T., III; Koelsch, G.; Shin, D.; Ghosh, A.K.; Tang, J. Crystal structure of memapsin 2 (beta-secretase) in complex with an inhibitor OM00-3. Biochemistry, 2002, 41(36), 10963-10967.
[http://dx.doi.org/10.1021/bi026232n] [PMID: 12206667]
(b) Liu, S.; Fu, R.; Cheng, X.; Chen, S-P.; Zhou, L.H. Exploring the binding of BACE-1 inhibitors using comparative binding energy analysis (COMBINE). BMC Struct. Biol., 2012, 12, 21.
[http://dx.doi.org/10.1186/1472-6807-12-21] [PMID: 22925713]
[18]
Andreeva, N.S.; Rumsh, L.D. Analysis of crystal structures of aspartic proteinases: on the role of amino acid residues adjacent to the catalytic site of pepsin-like enzymes. Protein Sci., 2001, 10(12), 2439-2450.
[http://dx.doi.org/10.1110/ps.ps.25801] [PMID: 11714911]
[19]
Barman, A.; Prabhakar, R. Computational insights into substrate and site specificities, catalytic mechanism, and protonation states of the catalytic Asp dyad of β-secretase. Scientifica, 2014, 2014p. 59872811
[20]
Huse, J.T.; Pijak, D.S.; Leslie, G.J.; Lee, V.M.; Doms, R.W. Maturation and endosomal targeting of β-site amyloid precursor protein-cleaving enzyme. The Alzheimer’s disease β-secretase. J. Biol. Chem., 2000, 275(43), 33729-33737.
[http://dx.doi.org/10.1074/jbc.M004175200] [PMID: 10924510]
[21]
Koo, E.H.; Squazzo, S.L. Evidence that production and release of amyloid beta-protein involves the endocytic pathway. J. Biol. Chem., 1994, 269(26), 17386-17389.
[PMID: 8021238]
[22]
Sobhanifar, S.; Schneider, B.; Löhr, F.; Gottstein, D.; Ikeya, T.; Mlynarczyk, K.; Pulawski, W.; Ghoshdastider, U.; Kolinski, M.; Filipek, S.; Güntert, P.; Bernhard, F.; Dötsch, V. Structural investigation of the C-terminal catalytic fragment of presenilin 1. Proc. Natl. Acad. Sci. USA, 2010, 107(21), 9644-9649.
[http://dx.doi.org/10.1073/pnas.1000778107] [PMID: 20445084]
[23]
Kaether, C.; Haass, C.; Steiner, H. Assembly, trafficking and function of gamma-secretase. Neurodegener. Dis., 2006, 3(4-5), 275-283.
[http://dx.doi.org/10.1159/000095267] [PMID: 17047368]
[24]
Zhou, S.; Zhou, H.; Walian, P.J.; Jap, B.K. The discovery and role of CD147 as a subunit of gamma-secretase complex. Drug News Perspect., 2006, 19(3), 133-138.
[http://dx.doi.org/10.1358/dnp.2006.19.3.985932] [PMID: 16804564]
[25]
Zhou, S.; Zhou, H.; Walian, P.J.; Jap, B.K. CD147 is a regulatory subunit of the γ-secretase complex in Alzheimer’s disease amyloid β-peptide production. Proc. Natl. Acad. Sci. USA, 2005, 102(21), 7499-7504.
[http://dx.doi.org/10.1073/pnas.0502768102] [PMID: 15890777]
[26]
Chen, F.; Hasegawa, H.; Schmitt-Ulms, G.; Kawarai, T.; Bohm, C.; Katayama, T.; Gu, Y.; Sanjo, N.; Glista, M.; Rogaeva, E.; Wakutani, Y.; Pardossi-Piquard, R.; Ruan, X.; Tandon, A.; Checler, F.; Marambaud, P.; Hansen, K.; Westaway, D.; St George-Hyslop, P.; Fraser, P. TMP21 is a presenilin complex component that modulates gamma-secretase but not epsilon-secretase activity. Nature, 2006, 440(7088), 1208-1212.
[http://dx.doi.org/10.1038/nature04667] [PMID: 16641999]
[27]
Farfara, D.; Trudler, D.; Segev-Amzaleg, N.; Galron, R.; Stein, R.; Frenkel, D. γ-Secretase component presenilin is important for microglia β-amyloid clearance. Ann. Neurol., 2011, 69(1), 170-180.
[http://dx.doi.org/10.1002/ana.22191] [PMID: 21280087]
[28]
Zhang, Y.W.; Luo, W.J.; Wang, H.; Lin, P.; Vetrivel, K.S.; Liao, F.; Li, F.; Wong, P.C.; Farquhar, M.G.; Thinakaran, G.; Xu, H. Nicastrin is critical for stability and trafficking but not association of other presenilin/γ-secretase components. J. Biol. Chem., 2005, 280(17), 17020-17026.
[http://dx.doi.org/10.1074/jbc.M409467200] [PMID: 15711015]
[29]
Prokop, S.; Shirotani, K.; Edbauer, D.; Haass, C.; Steiner, H. Requirement of PEN-2 for stabilization of the presenilin N-/C-terminal fragment heterodimer within the gamma-secretase complex. J. Biol. Chem., 2004, 279(22), 23255-23261.
[http://dx.doi.org/10.1074/jbc.M401789200] [PMID: 15039426]
[30]
Lee, S.F.; Shah, S.; Yu, C.; Wigley, W.C.; Li, H.; Lim, M.; Pedersen, K.; Han, W.; Thomas, P.; Lundkvist, J.; Hao, Y.H.; Yu, G. A conserved GXXXG motif in APH-1 is critical for assembly and activity of the gamma-secretase complex. J. Biol. Chem., 2004, 279(6), 4144-4152.
[http://dx.doi.org/10.1074/jbc.M309745200] [PMID: 14627705]
[31]
He, G.; Luo, W.; Li, P.; Remmers, C.; Netzer, W.J.; Hendrick, J.; Bettayeb, K.; Flajolet, M.; Gorelick, F.; Wennogle, L.P.; Greengard, P. Gamma-secretase activating protein is a therapeutic target for Alzheimer’s disease. Nature, 2010, 467(7311), 95-98.
[http://dx.doi.org/10.1038/nature09325] [PMID: 20811458]
[32]
Zhang, X.; Li, Y.; Xu, H.; Zhang, Y-W. The γ-secretase complex: from structure to function. Front. Cell. Neurosci., 2014, 8, 427.
[http://dx.doi.org/10.3389/fncel.2014.00427] [PMID: 25565961]
[33]
Wong, G.T.; Manfra, D.; Poulet, F.M.; Zhang, Q.; Josien, H.; Bara, T.; Engstrom, L.; Pinzon-Ortiz, M.; Fine, J.S.; Lee, H.J.; Zhang, L.; Higgins, G.A.; Parker, E.M. Chronic treatment with the gamma-secretase inhibitor LY-411,575 inhibits beta-amyloid peptide production and alters lymphopoiesis and intestinal cell differentiation. J. Biol. Chem., 2004, 279(13), 12876-12882.
[http://dx.doi.org/10.1074/jbc.M311652200] [PMID: 14709552]
[34]
Haapasalo, A.; Kovacs, D.M. The many substrates of presenilin/γ-secretase. J. Alzheimers Dis., 2011, 25(1), 3-28.
[http://dx.doi.org/10.3233/JAD-2011-101065] [PMID: 21335653]
[35]
Imbimbo, B.P.; Panza, F.; Frisardi, V.; Solfrizzi, V.; D’Onofrio, G.; Logroscino, G.; Seripa, D.; Pilotto, A. Therapeutic intervention for Alzheimer’s disease with γ-secretase inhibitors: still a viable option? Expert Opin. Investig. Drugs, 2011, 20(3), 325-341.
[http://dx.doi.org/10.1517/13543784.2011.550572] [PMID: 21222550]
[36]
Schor, N.F. What the halted phase III γ-secretase inhibitor trial may (or may not) be telling us. Ann. Neurol., 2011, 69(2), 237-239.
[http://dx.doi.org/10.1002/ana.22365] [PMID: 21387368]
[37]
Tamayev, R.; D’Adamio, L. Inhibition of gamma-secretase worsens memory deficits in a genetically congruous mouse model of Danish dementia. Mol. Neurodegener., 2012, 7, 19.
[38]
Crump, C.J.; Johnson, D.S.; Li, Y.M. Development and mechanism of γ-secretase modulators for Alzheimer’s disease. Biochemistry, 2013, 52(19), 3197-3216.
[http://dx.doi.org/10.1021/bi400377p] [PMID: 23614767]
[39]
Cleveland, D.W.; Hwo, S.Y.; Kirschner, M.W. Physical and chemical properties of purified tau factor and the role of tau in microtubule assembly. J. Mol. Biol., 1977, 116(2), 227-247.
[http://dx.doi.org/10.1016/0022-2836(77)90214-5] [PMID: 146092]
[40]
von Bergen, M.; Barghorn, S.; Biernat, J.; Mandelkow, E.M.; Mandelkow, E. Tau aggregation is driven by a transition from random coil to beta sheet structure. Biochim. Biophys. Acta, 2005, 1739(2-3), 158-166.
[http://dx.doi.org/10.1016/j.bbadis.2004.09.010] [PMID: 15615635]
[41]
Gamblin, T.C. Potential structure/function relationships of predicted secondary structural elements of tau. Biochim. Biophys. Acta, 2005, 1739(2-3), 140-149.
[http://dx.doi.org/10.1016/j.bbadis.2004.08.013] [PMID: 15615633]
[42]
Jeganathan, S.; von Bergen, M.; Mandelkow, E.M.; Mandelkow, E. The natively unfolded character of tau and its aggregation to Alzheimer-like paired helical filaments. Biochemistry, 2008, 47(40), 10526-10539.
[http://dx.doi.org/10.1021/bi800783d] [PMID: 18783251]
[43]
Dyson, H.J.; Wright, P.E. Intrinsically unstructured proteins and their functions. Nat. Rev. Mol. Cell Biol., 2005, 6(3), 197-208.
[http://dx.doi.org/10.1038/nrm1589] [PMID: 15738986]
[44]
Alonso, A.; Zaidi, T.; Novak, M.; Grundke-Iqbal, I.; Iqbal, K. Hyperphosphorylation induces self-assembly of τ into tangles of paired helical filaments/straight filaments. Proc. Natl. Acad. Sci. USA, 2001, 98(12), 6923-6928.
[http://dx.doi.org/10.1073/pnas.121119298] [PMID: 11381127]
[45]
Sergeant, N.; Bretteville, A.; Hamdane, M.; Caillet-Boudin, M.L.; Grognet, P.; Bombois, S.; Blum, D.; Delacourte, A.; Pasquier, F.; Vanmechelen, E.; Schraen-Maschke, S.; Buée, L. Biochemistry of Tau in Alzheimer’s disease and related neurological disorders. Expert Rev. Proteomics, 2008, 5(2), 207-224.
[http://dx.doi.org/10.1586/14789450.5.2.207] [PMID: 18466052]
[46]
Kolarova, M.; García-Sierra, F.; Bartos, A.; Ricny, J.; Ripova, D. Structure and pathology of tau protein in Alzheimer disease. Int. J. Alzheimers Dis., 2012, 2012, 731526
[http://dx.doi.org/10.1155/2012/731526] [PMID: 22690349]
[47]
Grundke-Iqbal, I.; Iqbal, K.; Tung, Y.C.; Quinlan, M.; Wisniewski, H.M.; Binder, L.I. Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc. Natl. Acad. Sci. USA, 1986, 83(13), 4913-4917.
[http://dx.doi.org/10.1073/pnas.83.13.4913] [PMID: 3088567]
[48]
Grundke-Iqbal, I.; Iqbal, K.; Quinlan, M.; Tung, Y.C.; Zaidi, M.S.; Wisniewski, H.M. Microtubule-associated protein tau. A component of Alzheimer paired helical filaments. J. Biol. Chem., 1986, 261(13), 6084-6089.
[PMID: 3084478]
[49]
Iqbal, K.; Grundke-Iqbal, I.; Smith, A.J.; George, L.; Tung, Y.C.; Zaidi, T. Identification and localization of a tau peptide to paired helical filaments of Alzheimer disease. Proc. Natl. Acad. Sci. USA, 1989, 86(14), 5646-5650.
[http://dx.doi.org/10.1073/pnas.86.14.5646] [PMID: 2501795]
[50]
Iqbal, K.; Grundke-Iqbal, I.; Zaidi, T.; Merz, P.A.; Wen, G.Y.; Shaikh, S.S.; Wisniewski, H.M.; Alafuzoff, I.; Winblad, B. Defective brain microtubule assembly in Alzheimer’s disease. Lancet, 1986, 2(8504), 421-426.
[http://dx.doi.org/10.1016/S0140-6736(86)92134-3] [PMID: 2874414]
[51]
Lee, V.M.; Balin, B.J.; Otvos, L., Jr; Trojanowski, J.Q. A68: a major subunit of paired helical filaments and derivatized forms of normal Tau. Science, 1991, 251(4994), 675-678.
[http://dx.doi.org/10.1126/science.1899488] [PMID: 1899488]
[52]
Goedert, M.; Spillantini, M.G.; Cairns, N.J.; Crowther, R.A. Tau proteins of Alzheimer paired helical filaments: abnormal phosphorylation of all six brain isoforms. Neuron, 1992, 8(1), 159-168.
[http://dx.doi.org/10.1016/0896-6273(92)90117-V] [PMID: 1530909]
[53]
Alonso, A.C.; Zaidi, T.; Grundke-Iqbal, I.; Iqbal, K. Role of abnormally phosphorylated tau in the breakdown of microtubules in Alzheimer disease. Proc. Natl. Acad. Sci. USA, 1994, 91(12), 5562-5566.
[http://dx.doi.org/10.1073/pnas.91.12.5562] [PMID: 8202528]
[54]
Jicha, G.A.; Lane, E.; Vincent, I.; Otvos, L., Jr; Hoffmann, R.; Davies, P. A conformation- and phosphorylation-dependent antibody recognizing the paired helical filaments of Alzheimer’s disease. J. Neurochem., 1997, 69(5), 2087-2095.
[http://dx.doi.org/10.1046/j.1471-4159.1997.69052087.x] [PMID: 9349554]
[55]
Jicha, G.A.; Berenfeld, B.; Davies, P. Sequence requirements for formation of conformational variants of tau similar to those found in Alzheimer’s disease. J. Neurosci. Res., 1999, 55(6), 713-723.
[http://dx.doi.org/10.1002/(SICI)1097-4547(19990315)55:6<713:AID-JNR6>3.0.CO;2-G] [PMID: 10220112]
[56]
Jicha, G.A.; Rockwood, J.M.; Berenfeld, B.; Hutton, M.; Davies, P. Altered conformation of recombinant frontotemporal dementia-17 mutant tau proteins. Neurosci. Lett., 1999, 260(3), 153-156.
[http://dx.doi.org/10.1016/S0304-3940(98)00980-X] [PMID: 10076890]
[57]
Novak, M.; Jakes, R.; Edwards, P.C.; Milstein, C.; Wischik, C.M. Difference between the tau protein of Alzheimer paired helical filament core and normal tau revealed by epitope analysis of monoclonal antibodies 423 and 7.51. Proc. Natl. Acad. Sci. USA, 1991, 88(13), 5837-5841.
[http://dx.doi.org/10.1073/pnas.88.13.5837] [PMID: 1712107]
[58]
Gamblin, T.C.; Chen, F.; Zambrano, A.; Abraha, A.; Lagalwar, S.; Guillozet, A.L.; Lu, M.; Fu, Y.; Garcia-Sierra, F.; LaPointe, N.; Miller, R.; Berry, R.W.; Binder, L.I.; Cryns, V.L. Caspase cleavage of tau: linking amyloid and neurofibrillary tangles in Alzheimer’s disease. Proc. Natl. Acad. Sci. USA, 2003, 100(17), 10032-10037.
[http://dx.doi.org/10.1073/pnas.1630428100] [PMID: 12888622]
[59]
Cotman, C.W.; Poon, W.W.; Rissman, R.A.; Blurton-Jones, M. The role of caspase cleavage of tau in Alzheimer disease neuropathology. J. Neuropathol. Exp. Neurol., 2005, 64(2), 104-112.
[http://dx.doi.org/10.1093/jnen/64.2.104] [PMID: 15751224]
[60]
Brandt, R.; Lee, G. Functional organization of microtubule-associated protein tau. Identification of regions which affect microtubule growth, nucleation, and bundle formation in vitro. J. Biol. Chem., 1993, 268(5), 3414-3419.
[PMID: 8429017]
[61]
Ghosh, A.K.; Shin, D.; Downs, D.; Koelsch, G.; Lin, X.; Ermolieff, J.; Tang, J. Design of potent inhibitors for human brain memapsin 2 (β-secretase). J. Am. Chem. Soc., 2000, 122(14), 3522-3523.
[http://dx.doi.org/10.1021/ja000300g] [PMID: 30443047]
[62]
Moussa-Pacha, N.M.; Abdin, S.M.; Omar, H.A.; Alniss, H.; Al-Tel, T.H.; Al‐Tel, T.H. BACE1 inhibitors: Current status and future directions in treating Alzheimer’s disease. Med. Res. Rev., 2020, 40(1), 339-384.
[http://dx.doi.org/10.1002/med.21622] [PMID: 31347728]
[63]
Coimbra, J.R.M.; Marques, D.F.F.; Baptista, S.J.; Pereira, C.M.F.; Moreira, P.I.; Dinis, T.C.P.; Santos, A.E.; Salvador, J.A.R. Highlights in BACE1 inhibitors for Alzheimer’s disease treatment. Front Chem., 2018, 6, 178.
[http://dx.doi.org/10.3389/fchem.2018.00178] [PMID: 29881722]
[64]
Ghosh, A.K.; Hong, L.; Tang, J. Beta-secretase as a therapeutic target for inhibitor drugs. Curr. Med. Chem., 2002, 9(11), 1135-1144.
[http://dx.doi.org/10.2174/0929867023370149] [PMID: 12052177]
[65]
Ermolieff, J.; Loy, J.A.; Koelsch, G.; Tang, J. Proteolytic activation of recombinant pro-memapsin 2 (pro-beta-secretase) studied with new fluorogenic substrates. Biochemistry, 2000, 39(40), 12450-12456.
[http://dx.doi.org/10.1021/bi001494f] [PMID: 11015226]
[66]
Turner, R.T., III; Koelsch, G.; Hong, L.; Castanheira, P.; Ermolieff, J.; Ghosh, A.K.; Tang, J. Subsite specificity of memapsin 2 (beta-secretase): implications for inhibitor design. Biochemistry, 2001, 40(34), 10001-10006.
[http://dx.doi.org/10.1021/bi015546s] [PMID: 11513577]
[67]
Hom, R.K.; Fang, L.Y.; Mamo, S.; Tung, J.S.; Guinn, A.C.; Walker, D.E.; Davis, D.L.; Gailunas, A.F.; Thorsett, E.D.; Sinha, S.; Knops, J.E.; Jewett, N.E.; Anderson, J.P.; John, V. Design and synthesis of statine-based cell-permeable peptidomimetic inhibitors of human β-secretase. J. Med. Chem., 2003, 46(10), 1799-1802.
[http://dx.doi.org/10.1021/jm025619l] [PMID: 12723942]
[68]
Brady, S.F.; Singh, S.; Crouthamel, M.C.; Holloway, M.K.; Coburn, C.A.; Garsky, V.M.; Bogusky, M.; Pennington, M.W.; Vacca, J.P.; Hazuda, D.; Lai, M.T. Rational design and synthesis of selective BACE-1 inhibitors. Bioorg. Med. Chem. Lett., 2004, 14(3), 601-604.
[http://dx.doi.org/10.1016/j.bmcl.2003.11.061] [PMID: 14741251]
[69]
Iserloh, U.; Pan, J.; Stamford, A.W.; Kennedy, M.E.; Zhang, Q.; Zhang, L.; Parker, E.M.; McHugh, N.A.; Favreau, L.; Strickland, C.; Voigt, J. Discovery of an orally efficaceous 4-phenoxypyrrolidine-based BACE-1 inhibitor. Bioorg. Med. Chem. Lett., 2008, 18(1), 418-422.
[http://dx.doi.org/10.1016/j.bmcl.2007.10.053] [PMID: 17980584]
[70]
Cumming, J.; Babu, S.; Huang, Y.; Carrol, C.; Chen, X.; Favreau, L.; Greenlee, W.; Guo, T.; Kennedy, M.; Kuvelkar, R.; Le, T.; Li, G.; McHugh, N.; Orth, P.; Ozgur, L.; Parker, E.; Saionz, K.; Stamford, A.; Strickland, C.; Tadesse, D.; Voigt, J.; Zhang, L.; Zhang, Q. Piperazine sulfonamide BACE1 inhibitors: design, synthesis, and in vivo characterization. Bioorg. Med. Chem. Lett., 2010, 20(9), 2837-2842.
[http://dx.doi.org/10.1016/j.bmcl.2010.03.050] [PMID: 20347593]
[71]
Probst, G.; Xu, Y.Z. Small-molecule BACE1 inhibitors: a patent literature review (2006 - 2011). Exp Opin. Ther. Pat., 2012, 22, 511-540.
[72]
Evin, G.; Lessene, G.; Wilkins, S. BACE inhibitors as potential drugs for the treatment of Alzheimer’s disease: focus on bioactivity. Recent Patents CNS Drug Discov., 2011, 6(2), 91-106.
[http://dx.doi.org/10.2174/157488911795933938] [PMID: 21585329]
[73]
Vassar, R. BACE1 inhibitor drugs in clinical trials for Alzheimer’s disease. Alzheimers Res. Ther., 2014, 6(9), 89.
[http://dx.doi.org/10.1186/s13195-014-0089-7] [PMID: 25621019]
[74]
Martenyi, F.; Dean, R.A.; Lowe, S.; Nakano, M.; Monk, S.; Willis, B.A.; Gonzales, C.; Mergott, D.; Leslie, D.; May, P.; James, A.; Gevorkyan, H.; Jhee, S.; Ereshefsky, L.; Citron, M. BACE inhibitor LY2886721 safety and central and peripheral PK and PD in healthy subjects (HSs). Alzheimers Dement., 2012, 8, 583-P584.
[http://dx.doi.org/10.1016/j.jalz.2012.05.1588]
[75]
Forman, M.; Palcza, J.; Tseng, J.; Leempoels, J.; Ramael, S.; Han, D.; Jhee, S.; Ereshefsky, L.; Tanen, M.; Laterza, O.; Dockendorf, M.; Krishna, G.; Ma, L.; Wagner, J.; Troyer, M. The novel BACE inhibitor MK-8931 dramatically lowers cerebrospinal fluid Aβ peptides in health subjects following single- and multiple-dose administration. Alzheimers Dement., 2012, 8, 704.
[http://dx.doi.org/10.1016/j.jalz.2012.05.1900]
[76]
Alexander, R.; Budd, S.; Russell, M.; Kugler, A.; Cebers, G.; Ye, N.; Olsson, T.; Burdette, D.; Maltby, J.; Paraskos, J.; Elsby, K.; Han, D.; Goldwater, R.; Ereshefsky, L. AZD3293 a novel BACE1 inhibitor: safety, tolerability and effects on plasma and CSF Ab peptides following single- and multiple-dose administration. Neurobiol. Aging, 2014, 35, S2.
[http://dx.doi.org/10.1016/j.neurobiolaging.2014.01.033]
[77]
Lai, R.; Albala, B.; Kaplow, J.M.; Aluri, J.; Yen, M.; Satlin, A. First-in-human study of E2609, a novel BACE1 inhibitor, demonstrates prolonged reductions in plasma beta-amyloid levels after single dosing. Alzheimers Dement., 2012, 8, 96.
[http://dx.doi.org/10.1016/j.jalz.2012.05.237]
[78]
Lai, R.; Albala, B.; Kaplow, J.M.; Majid, O.; Matijevic, M.; Aluri, J.; Satlin, A. Novel BACE1 inhibitor E2609 reduces plasma and CSF amyloid in health subjects after 14 days oral administration.The 11th International Conference on Alzheimer’s & Parkinson’s Diseases; Florence, Italy, March 6-10, 2013.
[79]
Bernier, F.; Sato, Y.; Matijevic, M.; Desmond, H.; McGrath, S.; Burns, L.; Kaplow, J.M.; Albala, B. Clinical study of E2609, a novel BACE1 inhibitor, demonstrates target engagement and inhibition of BACE1 activity in CSF. Alzheimers Dement., 2013, 9, 886.
[http://dx.doi.org/10.1016/j.jalz.2013.08.244]
[80]
Neumann, U.; Ufer, M.; Jacobson, L.H.; Rouzade-Dominguez, M.L.; Huledal, G.; Kolly, C.; Lüönd, R.M.; Machauer, R.; Veenstra, S.J.; Hurth, K.; Rueeger, H.; Tintelnot-Blomley, M.; Staufenbiel, M.; Shimshek, D.R.; Perrot, L.; Frieauff, W.; Dubost, V.; Schiller, H.; Vogg, B.; Beltz, K.; Avrameas, A.; Kretz, S.; Pezous, N.; Rondeau, J.M.; Beckmann, N.; Hartmann, A.; Vormfelde, S.; David, O.J.; Galli, B.; Ramos, R.; Graf, A.; Lopez Lopez, C. The BACE-1 inhibitor CNP520 for prevention trials in Alzheimer’s disease. EMBO Mol. Med., 2018, 10(11), e9316
[http://dx.doi.org/10.15252/emmm.201809316] [PMID: 30224383]
[81]
Dobrowolska Zakaria, J.A.; Vassar, R.J. A promising, novel, and unique BACE1 inhibitor emerges in the quest to prevent Alzheimer’s disease. EMBO Mol. Med., 2018, 10(11), e9717
[http://dx.doi.org/10.15252/emmm.201809717] [PMID: 30322841]
[82]
Dislich, B.; Lichtenthaler, S.F. The membrane-bound aspartyl protease BACE1: molecular and functional properties in Alzheimer’s disease and beyond. Front. Physiol., 2012, 3, 8.
[http://dx.doi.org/10.3389/fphys.2012.00008] [PMID: 22363289]
[83]
Yuan, J.; Venkatraman, S.; Zheng, Y.; McKeever, B.M.; Dillard, L.W.; Singh, S.B. Structure-based design of β-site APP cleaving enzyme 1 (BACE1) inhibitors for the treatment of Alzheimer’s disease. J. Med. Chem., 2013, 56(11), 4156-4180.
[http://dx.doi.org/10.1021/jm301659n] [PMID: 23509904]
[84]
Vassar, R. BACE1 inhibition as a therapeutic strategy for Alzheimer’s disease. J. Sport Health Sci., 2016, 5(4), 388-390.
[http://dx.doi.org/10.1016/j.jshs.2016.10.004] [PMID: 30356583]
[85]
Shah, N.P.; Solanki, V.S.; Gurjar, A.S. Advancements in BACE1 and non-peptide bACE1 inhibitors for Alzheimer’s disease. Indian J. Chem., 2018, 57B, 830-842.
[86]
Huang, W.; Yu, H.; Sheng, R.; Li, J.; Hu, Y. Identification of pharmacophore model, synthesis and biological evaluation of N-phenyl-1-arylamide and N-phenylbenzenesulfonamide derivatives as BACE 1 inhibitors. Bioorg. Med. Chem., 2008, 16(24), 10190-10197.
[http://dx.doi.org/10.1016/j.bmc.2008.10.059] [PMID: 19013073]
[87]
Hamada, Y. Drug discovery of β-secretase inhibitors based on quantum chemical interactions for the treatment of Alzheimer’s disease. SOJ Pharm. Pharm. Sci., 2014, 1, 1-8.
[http://dx.doi.org/10.15226/2374-6866/1/3/00118]
[88]
Hamada, Y.; Kiso, Y. Discovery of BACE1 inhibitors for the treatment of Alzheimer’s disease; Intech: London, 2017.
[89]
Pandey, Y.S.; Gupta, S.P. Design of some new potent beta-secretase inhibitors based on QSAR and molecular modeling study on a series of hydroxyethylamine derivatives. Lett. Drug Des. Discov., 2013, 10, 253-265.
[90]
Truong, A.P.; Tóth, G.; Probst, G.D.; Sealy, J.M.; Bowers, S.; Wone, D.W.; Dressen, D.; Hom, R.K.; Konradi, A.W.; Sham, H.L.; Wu, J.; Peterson, B.T.; Ruslim, L.; Bova, M.P.; Kholodenko, D.; Motter, R.N.; Bard, F.; Santiago, P.; Ni, H.; Chian, D.; Soriano, F.; Cole, T.; Brigham, E.F.; Wong, K.; Zmolek, W.; Goldbach, E.; Samant, B.; Chen, L.; Zhang, H.; Nakamura, D.F.; Quinn, K.P.; Yednock, T.A.; Sauer, J.M. Design of an orally efficacious hydroxyethylamine (HEA) BACE-1 inhibitor in a preclinical animal model. Bioorg. Med. Chem. Lett., 2010, 20(21), 6231-6236.
[http://dx.doi.org/10.1016/j.bmcl.2010.08.102] [PMID: 20833041]
[91]
Molegro Bioinformatics Solution. Available from: http:// www.molegro.com
[92]
Arya, R.; Gupta, S.P.; Paliwal, S.; Sharma, S.; Madan, K.; Chauhan, M. Pharmacophore modeling and docking studies to investigate potential leads for the development of β-Secretase APP Cleavage Enzyme-1 (BACE-1) Inhibitors. Lett. Drug Des. Discov., 2019, 16, 775-784.
[http://dx.doi.org/10.2174/1570180815666181023110736]
[93]
Pandey, A.; Mungalpara, J.; Mohan, C.G. Comparative molecular field analysis and comparative molecular similarity indices analysis of hydroxyethylamine derivatives as selective human BACE-1 inhibitor. Mol. Divers., 2010, 14(1), 39-49.
[http://dx.doi.org/10.1007/s11030-009-9139-7] [PMID: 19330459]
[94]
Arya, R.; Gupta, S.P.; Paliwal, S.; Kesar, S.; Mishra, A.; Prabhakar, Y.S. QSAR and molecular modeling studies on a series of pyrrolidine analogs acting as BACE-1 Inhibitors. Lett. Drug Des. Discov., 2019, 16, 746-760.
[http://dx.doi.org/10.2174/1570180815666180627124422]
[95]
Iserloh, U.; Wu, Y.; Cumming, J.N.; Pan, J.; Wang, L.Y.; Stamford, A.W.; Kennedy, M.E.; Kuvelkar, R.; Chen, X.; Parker, E.M.; Strickland, C.; Voigt, J. Potent pyrrolidine- and piperidine-based BACE-1 inhibitors. Bioorg. Med. Chem. Lett., 2008, 18, 414-417.
[96]
Imbimbo, B.P.; Giardina, G.A.M. γ-secretase inhibitors and modulators for the treatment of Alzheimer’s disease: disappointments and hopes. Curr. Top. Med. Chem., 2011, 11(12), 1555-1570.
[http://dx.doi.org/10.2174/156802611795860942] [PMID: 21510832]
[97]
Eriksen, J.L.; Sagi, S.A.; Smith, T.E.; Weggen, S.; Das, P.; McLendon, D.C.; Ozols, V.V.; Jessing, K.W.; Zavitz, K.H.; Koo, E.H.; Golde, T.E. NSAIDs and enantiomers of flurbiprofen target gamma-secretase and lower Abeta 42 in vivo. J. Clin. Invest., 2003, 112(3), 440-449.
[http://dx.doi.org/10.1172/JCI18162] [PMID: 12897211]
[98]
Miguel-Álvarez, M.; Santos-Lozano, A.; Sanchis-Gomar, F.; Fiuza-Luces, C.; Pareja-Galeano, H.; Garatachea, N.; Lucia, A. Non-steroidal anti-inflammatory drugs as a treatment for Alzheimer’s disease: a systematic review and meta-analysis of treatment effect. Drugs Aging, 2015, 32(2), 139-147.
[http://dx.doi.org/10.1007/s40266-015-0239-z] [PMID: 25644018]
[99]
Pasqualetti, P.; Bonomini, C.; Dal Forno, G.; Paulon, L.; Sinforiani, E.; Marra, C.; Zanetti, O.; Rossini, P.M. A randomized controlled study on effects of ibuprofen on cognitive progression of Alzheimer’s disease. Aging Clin. Exp. Res., 2009, 21(2), 102-110.
[http://dx.doi.org/10.1007/BF03325217] [PMID: 19448381]
[100]
Folch, J.; Petrov, D.; Ettcheto, M.; Abad, S.; Sánchez-López, E.; García, M.L.; Olloquequi, J.; Beas-Zarate, C.; Auladell, C.; Camins, A. Current research therapeutic strategies for Alzheimer’s disease treatment. Neural Plast., 2016, 2016, 8501693
[http://dx.doi.org/10.1155/2016/8501693] [PMID: 26881137]
[101]
Tang, N.; Somavarapu, A.K.; Kepp, K.P. Molecular recipe for γ-secretase modulation from computational analysis of 60 active compounds. ACS Omega, 2018, 3, 18078-18088.
[http://dx.doi.org/10.1021/acsomega.8b02196]
[102]
Bursavich, M.G.; Harrison, B.A.; Acharya, R.; Costa, D.E.; Freeman, E.A.; Hodgdon, H.E.; Hrdlicka, L.A.; Jin, H.; Kapadnis, S.; Moffit, J.S. Design, synthesis, and evaluation of a novel series of oxadiazine gamma-secretase modulators for familial Alzheimer’s Disease. J. Med. Chem., 2017, 60, 2383-2400.
[103]
Tomita, T.; Maruyama, K.; Saido, T.C.; Kume, H.; Shinozaki, K.; Tokuhiro, S.; Capell, A.; Walter, J.; Grunberg, J.; Haass, C.; Iwatsubo, T.; Obata, K. The presenilin 2 mutation (N141I) linked to familial Alzheimer disease (Volga German families) increases the secretion of amyloid protein ending at the 42nd (or 43rd) residue. Proc. Natl. Acad. Sci. U.S.A., 1997, 94, 2025-2030.
[104]
Mobley, D.L.; Dill, K.A. Binding of small-molecule ligands to proteins: “what you see” is not always “what you get”. Structure, 2009, 17, 489-498.
[105]
Bhadoriya, K.S.; Sharma, M.C.; Sharma, S.; Jain, S.V.; Avchar, M.H. An approach to design potent anti-Alzheimer’s agents by 3D-QSAR studies on fused 5,6-bicyclicheterocycles as c-secretase modulators using kNN–MFA methodology. Arab. J. Chem., 2014, 7, 924-935.
[http://dx.doi.org/10.1016/j.arabjc.2013.02.002]
[106]
Parker, M.F.; Barten, D.M.; Bergstrom, C.P.; Bronson, J.J.; Corsa, J.A.; Deshpande, M.S.; Felsenstein, K.M.; Guss, V.L.; Hansel, S.B.; Johnson, G.; Keavy, D.J.; Lau, W.Y.; Mock, J.; Prasad, C.V.; Polson, C.T.; Sloan, C.P.; Smith, D.W.; Wallace, O.B.; Wang, H.H.; Williams, A.; Zheng, M. N-(5-chloro-2-(hydroxymethyl)-N-alkyl-arylsulfonamides as γ-secretase inhibitors. Bioorg. Med. Chem. Lett., 2007, 17(16), 4432-4436.
[http://dx.doi.org/10.1016/j.bmcl.2007.06.022] [PMID: 17606371]
[107]
Masand, N.; Gupta, S.P.; Khosa, R.L. Designing of selective γ–secretase inhibitory benzenesulfonamides through comparative in vitro and in silico analysis. Curr. Drug Discov. Technol., 2018, 15(1), 65-77.
[http://dx.doi.org/10.2174/1570163814666170713103440] [PMID: 28707599]
[108]
Masand, N.; Gupta, S.P.; Khosa, R.L. N-Substituted aryl sulphonamides as potential anti-Alzheimer’s agents: design, synthesis and biological Evaluation. Curr Comput Aided Drug Des, 2018, 14(4), 338-348.
[http://dx.doi.org/10.2174/1573409914666180604115425] [PMID: 29866012]
[109]
Masand, N.; Gupta, S.P.; Khosa, R.L.; Patil, V.M. Heterocyclic secretase inhibitors for the treatment of Alzheimer’s disease: An Overview. Cent. Nerv. Syst. Agents Med. Chem., 2015, 17, 3-25.
[http://dx.doi.org/10.2174/1570159X13666151029105752] [PMID: 26511918]
[110]
Cowan, C.M.; Mudher, A. Are tau aggregates toxic or protective in tauopathies? Front. Neurol., 2013, 4, 114.
[http://dx.doi.org/10.3389/fneur.2013.00114] [PMID: 23964266]
[111]
West, S.; Bhugra, P. Emerging drug targets for Aβ and tau in Alzheimer’s disease: a systematic review. Br. J. Clin. Pharmacol., 2015, 80(2), 221-234.
[http://dx.doi.org/10.1111/bcp.12621] [PMID: 25753046]
[112]
Shefet-Carasso, L.; Benhar, I. Antibody-targeted drugs and drug resistance--challenges and solutions. Drug Resist. Updat., 2015, 18, 36-46.
[http://dx.doi.org/10.1016/j.drup.2014.11.001] [PMID: 25476546]
[113]
Berk, C.; Paul, G.; Sabbagh, M. Investigational drugs in Alzheimer’s disease: current progress. Expert Opin. Investig. Drugs, 2014, 23(6), 837-846.
[http://dx.doi.org/10.1517/13543784.2014.905542] [PMID: 24702504]
[114]
Grüninger, F. Invited review: Drug development for tauopathies. Neuropathol. Appl. Neurobiol., 2015, 41(1), 81-96.
[http://dx.doi.org/10.1111/nan.12192] [PMID: 25354646]
[115]
Iqbal, K.; Gong, C.X.; Liu, F. Microtubule-associated protein tau as a therapeutic target in Alzheimer’s disease. Expert Opin. Ther. Targets, 2014, 18(3), 307-318.
[http://dx.doi.org/10.1517/14728222.2014.870156] [PMID: 24387228]
[116]
Gourmaud, S.; Paquet, C.; Dumurgier, J.; Pace, C.; Bouras, C.; Gray, F.; Laplanche, J.L.; Meurs, E.F.; Mouton-Liger, F.; Hugon, J. Increased levels of cerebrospinal fluid JNK3 associated with amyloid pathology: links to cognitive decline. J. Psychiatry Neurosci., 2015, 40(3), 151-161.
[http://dx.doi.org/10.1503/jpn.140062] [PMID: 25455349]
[117]
Yoon, S.O.; Park, D.J.; Ryu, J.C.; Ozer, H.G.; Tep, C.; Shin, Y.J.; Lim, T.H.; Pastorino, L.; Kunwar, A.J.; Walton, J.C.; Nagahara, A.H.; Lu, K.P.; Nelson, R.J.; Tuszynski, M.H.; Huang, K. JNK3 perpetuates metabolic stress induced by Aβ peptides. Neuron, 2012, 75(5), 824-837.
[http://dx.doi.org/10.1016/j.neuron.2012.06.024] [PMID: 22958823]
[118]
Kimura, T.; Ishiguro, K.; Hisanaga, S. Physiological and pathological phosphorylation of tau by Cdk5. Front. Mol. Neurosci., 2014, 7, 65.
[http://dx.doi.org/10.3389/fnmol.2014.00065] [PMID: 25076872]
[119]
Zhou, Q.; Wang, M.; Du, Y.; Zhang, W.; Bai, M.; Zhang, Z.; Li, Z.; Miao, J. Inhibition of c-Jun N-terminal kinase activation reverses Alzheimer disease phenotypes in APPswe/PS1dE9 mice. Ann. Neurol., 2015, 77(4), 637-654.
[http://dx.doi.org/10.1002/ana.24361] [PMID: 25611954]
[120]
Resnick, L.; Fennell, M. Targeting JNK3 for the treatment of neurodegenerative disorders. Drug Discov. Today, 2004, 9(21), 932-939.
[http://dx.doi.org/10.1016/S1359-6446(04)03251-9] [PMID: 15501728]
[121]
de la Torre, A.V.; Junyent, F.; Folch, J.; Pelegrí, C.; Vilaplana, J.; Auladell, C.; Beas-Zarate, C.; Pallàs, M.; Verdaguer, E.; Camins, A. GSK3β inhibition is involved in the neuroprotective effects of cyclin-dependent kinase inhibitors in neurons. Pharmacol. Res., 2012, 65(1), 66-73.
[http://dx.doi.org/10.1016/j.phrs.2011.08.006] [PMID: 21875668]
[122]
Jorda, E.G.; Verdaguer, E.; Canudas, A.M.; Jiménez, A.; Bruna, A.; Caelles, C.; Bravo, R.; Escubedo, E.; Pubill, D.; Camarasa, J.; Pallàs, M.; Camins, A. Neuroprotective action of flavopiridol, a cyclin-dependent kinase inhibitor, in colchicine-induced apoptosis. Neuropharmacology, 2003, 45(5), 672-683.
[http://dx.doi.org/10.1016/S0028-3908(03)00204-1] [PMID: 12941380]
[123]
Domínguez, J.M.; Fuertes, A.; Orozco, L.; del Monte-Millán, M.; Delgado, E.; Medina, M. Evidence for irreversible inhibition of glycogen synthase kinase-3β by tideglusib. J. Biol. Chem., 2012, 287(2), 893-904.
[http://dx.doi.org/10.1074/jbc.M111.306472] [PMID: 22102280]
[124]
Medina, M. An overview on the clinical development of tau-based therapeutics. Int. J. Mol. Sci., 2018, 19(4), 1160.
[http://dx.doi.org/10.3390/ijms19041160] [PMID: 29641484]
[125]
Hochgräfe, K.; Sydow, A.; Matenia, D.; Cadinu, D.; Könen, S.; Petrova, O.; Pickhardt, M.; Goll, P.; Morellini, F.; Mandelkow, E.; Mandelkow, E.M. Preventive methylene blue treatment preserves cognition in mice expressing full-length pro-aggregant human Tau. Acta Neuropathol. Commun., 2015, 3(1), 25.
[http://dx.doi.org/10.1186/s40478-015-0204-4] [PMID: 25958115]
[126]
Babic, T. The cholinergic hypothesis of Alzheimer’s disease: a review of progress. J. Neurol. Neurosurg. Psychiatry, 1999, 67(4), 558.
[http://dx.doi.org/10.1136/jnnp.67.4.558] [PMID: 10610396]
[127]
Chen, P.Y.; Tsai, C.T.; Ou, C.Y.; Hsu, W.T.; Jhuo, M.D.; Wu, C.H.; Shih, T.C.; Cheng, T.H.; Chung, J.G. Computational analysis of novel drugs designed for use as acetylcholinesterase inhibitors and histamine H3 receptor antagonists for Alzheimer’s disease by docking, scoring and de novo evolution. Mol. Med. Rep., 2012, 5(4), 1043-1048.
[http://dx.doi.org/10.3892/mmr.2012.757] [PMID: 22267207]
[128]
Ambure, P.; Kar, S.; Roy, K. Pharmacophore mapping-based virtual screening followed by molecular docking studies in search of potential acetylcholinesterase inhibitors as anti-Alzheimer’s agents. Biosystems, 2014, 116, 10-20.
[http://dx.doi.org/10.1016/j.biosystems.2013.12.002] [PMID: 24325852]
[129]
Clark, J.K.; Cowley, P.; Muir, A.W.; Palin, R.; Pow, E.; Prosser, A.B.; Taylor, R.; Zhang, M.Q. Quaternary salts of E2020 analogues as acetylcholinesterase inhibitors for the reversal of neuromuscular block. Bioorg. Med. Chem. Lett., 2002, 12(18), 2565-2568.
[http://dx.doi.org/10.1016/S0960-894X(02)00482-1] [PMID: 12182861]
[130]
Lee, J.H.; Lee, K.T.; Yang, J.H.; Baek, N.I.; Kim, D.K. Acetylcholinesterase inhibitors from the twigs of Vaccinium oldhami Miquel. Arch. Pharm. Res., 2004, 27(1), 53-56.
[http://dx.doi.org/10.1007/BF02980046] [PMID: 14969339]
[131]
Youkwan, J.; Sutthivaiyakit, S.; Sutthivaiyakit, P. Citrusosides A-D and furanocoumarins with cholinesterase inhibitory activity from the fruit peels of Citrus hystrix. J. Nat. Prod., 2010, 73(11), 1879-1883.
[http://dx.doi.org/10.1021/np100531x] [PMID: 20964319]
[132]
Awang, K.; Chan, G.; Litaudon, M.; Ismail, N.H.; Martin, M.T.; Gueritte, F. 4-Phenylcoumarins from Mesua elegans with acetylcholinesterase inhibitory activity. Bioorg. Med. Chem., 2010, 18(22), 7873-7877.
[http://dx.doi.org/10.1016/j.bmc.2010.09.044] [PMID: 20943395]
[133]
Nadri, H.; Pirali-Hamedani, M.; Shekarchi, M.; Abdollahi, M.; Sheibani, V.; Amanlou, M.; Shafiee, A.; Foroumadi, A. Design, synthesis and anticholinesterase activity of a novel series of 1-benzyl-4-((6-alkoxy-3-oxobenzofuran-2(3H)-ylidene) methyl) pyridinium derivatives. Bioorg. Med. Chem., 2010, 18(17), 6360-6366.
[http://dx.doi.org/10.1016/j.bmc.2010.07.012] [PMID: 20673725]
[134]
Chufarova, N.; Czarnecka, K.; Skibiński, R.; Cuchra, M.; Majsterek, I.; Szymański, P. New tacrine-acridine hybrids as promising multifunctional drugs for potential treatment of Alzheimer’s disease. Arch. Pharm. (Weinheim), 2018, 351(7), e1800050
[http://dx.doi.org/10.1002/ardp.201800050] [PMID: 29870588]
[135]
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(1), 496-506.
[http://dx.doi.org/10.1080/14756366.2018.1430691] [PMID: 29405075]
[136]
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.
[http://dx.doi.org/10.1016/j.ejmech.2018.07.056] [PMID: 30245401]
[137]
Jin, P.; Kim, J.A.; Choi, D.Y.; Lee, Y.J.; Jung, H.S.; Hong, J.T. Anti-inflammatory and anti-amyloidogenic effects of a small molecule, 2,4-bis(p-hydroxyphenyl)-2-butenal in Tg2576 Alzheimer’s disease mice model. J. Neuroinflammation, 2013, 10, 2.
[http://dx.doi.org/10.1186/1742-2094-10-2] [PMID: 23289709]
[138]
Xie, S.S.; Wang, X.B.; Li, J.Y.; Yang, L.; Kong, L.Y. Design, synthesis and evaluation of novel tacrine-coumarin hybrids as multifunctional cholinesterase inhibitors against Alzheimer’s disease. Eur. J. Med. Chem., 2013, 64, 540-553.
[http://dx.doi.org/10.1016/j.ejmech.2013.03.051] [PMID: 23685572]
[139]
Catto, M.; Pisani, L.; Leonetti, F.; Nicolotti, O.; Pesce, P.; Stefanachi, A.; Cellamare, S.; Carotti, A. Design, synthesis and biological evaluation of coumarin alkylamines as potent and selective dual binding site inhibitors of acetylcholinesterase. Bioorg. Med. Chem., 2013, 21(1), 146-152.
[http://dx.doi.org/10.1016/j.bmc.2012.10.045] [PMID: 23199476]
[140]
Khoobi, M.; Alipour, M.; Moradi, A.; Sakhteman, A.; Nadri, H.; Razavi, S.F.; Ghandi, M.; Foroumadi, A.; Shafiee, A. Design, synthesis, docking study and biological evaluation of some novel tetrahydrochromeno [3′,4′:5,6]pyrano[2,3-b]quinolin-6(7H)-one derivatives against acetyl- and butyrylcholinesterase. Eur. J. Med. Chem., 2013, 68, 291-300.
[http://dx.doi.org/10.1016/j.ejmech.2013.07.045] [PMID: 23988412]
[141]
Ali, M.A.; Yar, M.S.; Hasan, M.Z.; Ahsan, M.J.; Pandian, S. Design, synthesis and evaluation of novel 5,6-dimethoxy-1-oxo-2,3-dihydro-1H-2-indenyl-3,4-substituted phenyl methanone analogues. Bioorg. Med. Chem. Lett., 2009, 19(17), 5075-5077.
[http://dx.doi.org/10.1016/j.bmcl.2009.07.042] [PMID: 19643609]
[142]
Sharma, K. Cholinesterase inhibitors as Alzheimer’s therapeutics (Review). Mol. Med. Rep., 2019, 20(2), 1479-1487.
[PMID: 31257471]
[143]
Girek, M.; Szymański, P. Tacrine hybrids as multitarget directed ligands in Alzheimer’s disease: influence of chemical structures on biological activities. Chem. Pap., 2019, 73, 269-289.
[http://dx.doi.org/10.1007/s11696-018-0590-8]
[144]
Meng, Q.; Ru, J.; Zhang, G.; Shen, C.; Schmitmeier, S.; Bader, A. Re-evaluation of tacrine hepatotoxicity using gel entrapped hepatocytes. Toxicol. Lett., 2007, 168(2), 140-147.
[http://dx.doi.org/10.1016/j.toxlet.2006.11.009] [PMID: 17166674]
[145]
Minarini, A.; Milelli, A.; Simoni, E.; Rosini, M.; Bolognesi, M.L.; Marchetti, C.; Tumiatti, V. Multifunctional tacrine derivatives in Alzheimer’s disease. Curr. Top. Med. Chem., 2013, 13(15), 1771-1786.
[http://dx.doi.org/10.2174/15680266113139990136] [PMID: 23931443]
[146]
Huang, L.; Su, T.; Shan, W.; Luo, Z.; Sun, Y.; He, F.; Li, X. Inhibition of cholinesterase activity and amyloid aggregation by berberine-phenyl-benzoheterocyclic and tacrine-phenyl-benzoheterocyclic hybrids. Bioorg. Med. Chem., 2012, 20, 3038-3048.

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