Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Review Article

Multi-Target-Directed Ligands as an Effective Strategy for the Treatment of Alzheimer’s Disease

Author(s): Bhupinder Kumar, Amandeep Thakur, Ashish Ranjan Dwivedi, Rakesh Kumar* and Vinod Kumar*

Volume 29, Issue 10, 2022

Published on: 04 January, 2022

Page: [1757 - 1803] Pages: 47

DOI: 10.2174/0929867328666210512005508

Price: $65

conference banner
Abstract

Alzheimer’s disease (AD) is a complex neurological disorder and multiple pathological factors are believed to be involved in the genesis and progression of the disease. A number of hypothesis including Acetylcholinesterase, Monoamine oxidase, β- Amyloid, Tau protein etc. have been proposed for the initiation and progression of the disease. At present, acetylcholine esterase inhibitors and memantine (NMDAR antagonist) are the only approved therapy for the symptomatic management of AD. Most of these single-target drugs have miserably failed in the treatment or halting the progression of the disease. Multi-factorial diseases like AD require complex treatment strategies that involve simultaneous modulation of a network of interacting targets. Since last few years, Multi-Target-Directed Ligands (MTDLs) strategy, drugs that can simultaneously hit multiple targets, is being explored as an effective therapeutic approach for the treatment of AD. In the current review article, the authors have briefly described various pathogenic pathways associated with the AD. Importance of Multi-Target-Directed Ligands and their design strategies in recently reported articles have been discussed in detail. Potent leads identified through various structure-activity relationship studies and their drug like characteristics are described. Recently developed promising compounds have been summarized in the article. Some of these MTDLs with balanced activity profile against different targets have the potential to be developed as drug candidates for the treatment of AD.

Keywords: Alzheimer’s disease, acetylcholinesterase, monoamine oxidase, β-amyloid, multi-target directed ligands, MTDLs.

« Previous Next »
[1]
Goedert, M.; Spillantini, M.G. A century of Alzheimer’s disease. Science, 2006, 314(5800), 777-781.
[http://dx.doi.org/10.1126/science.1132814] [PMID: 17082447]
[2]
Association, A. 2017 Alzheimer’s disease facts and figures. Alzheimers Dement., 2017, 13(4), 325-373.
[http://dx.doi.org/10.1016/j.jalz.2017.02.001]
[3]
Association, A. 2018 Alzheimer’s disease facts and figures. Alzheimers Dement., 2018, 14(3), 367-429.
[http://dx.doi.org/10.1016/j.jalz.2018.02.001]
[4]
Cimler, R.; Maresova, P.; Kuhnova, J.; Kuca, K. Predictions of Alzheimer’s disease treatment and care costs in European countries. PLoS One, 2019, 14(1), e0210958.
[http://dx.doi.org/10.1371/journal.pone.0210958] [PMID: 30682120]
[5]
Dorfman, V.B.; Pasquini, L.; Riudavets, M.; López-Costa, J.J.; Villegas, A.; Troncoso, J.C.; Lopera, F.; Castaño, E.M.; Morelli, L. Differential cerebral deposition of IDE and NEP in sporadic and familial Alzheimer’s disease. Neurobiol. Aging, 2010, 31(10), 1743-1757.
[http://dx.doi.org/10.1016/j.neurobiolaging.2008.09.016] [PMID: 19019493]
[6]
Alzheimer, A. Über einen eigenartigen schweren Erkrankungsprozeβ der Hirnrincle. Neurol. Central., 1906, 25, 1134.
[7]
Masters, C.L.; Bateman, R. blennow K, Rowe CC, Sperling RA, Cummings JL. Alzheimer’s disease. Nat. Rev. Dis. Primers, 2015, 15059.
[8]
Association, A. 2013 Alzheimer’s disease facts and figures. Alzheimers Dement., 2013, 9(2), 208-245.
[http://dx.doi.org/10.1016/j.jalz.2013.02.003] [PMID: 23507120]
[9]
Imbimbo, B.P.; Lombard, J.; Pomara, N. Pathophysiology of Alzheimer’s disease. Neuroimaging Clin. N. Am., 2005, 15(4), 727-753. , ix.
[http://dx.doi.org/10.1016/j.nic.2005.09.009] [PMID: 16443487]
[10]
Perry, E. Acetylcholine and Alzheimer’s disease. Br. J. Psychiatry, 1988, 152(6), 737-740.
[http://dx.doi.org/10.1192/bjp.152.6.737] [PMID: 3048527]
[11]
Wisniewski, T.; Ghiso, J.; Frangione, B. Biology of A β amyloid in Alzheimer’s disease. Neurobiol. Dis., 1997, 4(5), 313-328.
[http://dx.doi.org/10.1006/nbdi.1997.0147] [PMID: 9440120]
[12]
Kung, H.F. The β-amyloid hypothesis in Alzheimer’s disease: Seeing is believing. ACS Med. Chem. Lett., 2012, 3(4), 265-267.
[http://dx.doi.org/10.1021/ml300058m] [PMID: 24936237]
[13]
Kennedy, B.P.; Ziegler, M.G.; Alford, M.; Hansen, L.A.; Thal, L.J.; Masliah, E. Early and persistent alterations in prefrontal cortex MAO A and B in Alzheimer’s disease. J. Neural Transm. (Vienna), 2003, 110(7), 789-801.
[http://dx.doi.org/10.1007/s00702-003-0828-6] [PMID: 12811639]
[14]
Šimić, G.; Babić Leko, M.; Wray, S.; Harrington, C.; Delalle, I.; Jovanov-Milošević, N.; Bažadona, D.; Buée, L.; de Silva, R.; Di Giovanni, G.; Wischik, C.; Hof, P.R. Tau protein hyperphosphorylation and aggregation in Alzheimer’s disease and other tauopathies, and possible neuroprotective strategies. Biomolecules, 2016, 6(1), 6.
[http://dx.doi.org/10.3390/biom6010006] [PMID: 26751493]
[15]
Smith, M.A.; Rottkamp, C.A.; Nunomura, A.; Raina, A.K.; Perry, G. Oxidative stress in Alzheimer’s disease. Biochim. Biophys. Acta, 2000, 1502(1), 139-144.
[http://dx.doi.org/10.1016/S0925-4439(00)00040-5] [PMID: 10899439]
[16]
Garcia-Alloza, M.; Gil-Bea, F.J.; Diez-Ariza, M.; Chen, C.P.; Francis, P.T.; Lasheras, B.; Ramirez, M.J. Cholinergic-serotonergic imbalance contributes to cognitive and behavioral symptoms in Alzheimer’s disease. Neuropsychologia, 2005, 43(3), 442-449.
[http://dx.doi.org/10.1016/j.neuropsychologia.2004.06.007] [PMID: 15707619]
[17]
Cummings, J.L.; Ross, W.; Absher, J.; Gornbein, J.; Hadjiaghai, L. Depressive symptoms in Alzheimer disease: Assessment and determinants. Alzheimer Dis. Assoc. Disord., 1995, 9(2), 87-93.
[http://dx.doi.org/10.1097/00002093-199509020-00005] [PMID: 7662328]
[18]
Müller, T.J.; Braun, R.; Ansorge, M. A novel three-component one-pot pyrimidine synthesis based upon a coupling-isomerization sequence. Org. Lett., 2000, 2(13), 1967-1970.
[http://dx.doi.org/10.1021/ol006046e] [PMID: 10891203]
[19]
Kumar, B.; Mantha, A.K.; Kumar, V. Recent developments on the structure–activity relationship studies of MAO inhibitors and their role in different neurological disorders. RSC Advances, 2016, 6(48), 42660-42683.
[http://dx.doi.org/10.1039/C6RA00302H]
[20]
Sano, M.; Ernesto, C.; Thomas, R.G.; Klauber, M.R.; Schafer, K.; Grundman, M.; Woodbury, P.; Growdon, J.; Cotman, C.W.; Pfeiffer, E.; Schneider, L.S.; Thal, L.J. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease. The Alzheimer’s Disease Cooperative Study. N. Engl. J. Med., 1997, 336(17), 1216-1222.
[http://dx.doi.org/10.1056/NEJM199704243361704] [PMID: 9110909]
[21]
Sugimoto, H.; Yamanishi, Y.; Iimura, Y.; Kawakami, Y. Donepezil hydrochloride (E2020) and other acetylcholinesterase inhibitors. Curr. Med. Chem., 2000, 7(3), 303-339.
[http://dx.doi.org/10.2174/0929867003375191] [PMID: 10637367]
[22]
Marco-Contelles, J.; do Carmo Carreiras, M.; Rodríguez, C.; Villarroya, M.; García, A.G. Synthesis and pharmacology of galantamine. Chem. Rev., 2006, 106(1), 116-133.
[http://dx.doi.org/10.1021/cr040415t] [PMID: 16402773]
[23]
Anand, P.; Singh, B. A review on cholinesterase inhibitors for Alzheimer’s disease. Arch. Pharm. Res., 2013, 36(4), 375-399.
[http://dx.doi.org/10.1007/s12272-013-0036-3] [PMID: 23435942]
[24]
Gura, T. Hope in Alzheimer’s fight emerges from unexpected places. Nat. Med., 2008, 14(9), 894.
[http://dx.doi.org/10.1038/nm0908-894] [PMID: 18776868]
[25]
Racchi, M.; Mazzucchelli, M.; Porrello, E.; Lanni, C.; Govoni, S. Acetylcholinesterase inhibitors: Novel activities of old molecules. Pharmacol. Res., 2004, 50(4), 441-451.
[http://dx.doi.org/10.1016/j.phrs.2003.12.027] [PMID: 15304241]
[26]
Muñoz-Torrero, D. Acetylcholinesterase inhibitors as disease-modifying therapies for Alzheimer’s disease. Curr. Med. Chem., 2008, 15(24), 2433-2455.
[http://dx.doi.org/10.2174/092986708785909067] [PMID: 18855672]
[27]
Matsuzono, K.; Hishikawa, N.; Ohta, Y.; Yamashita, T.; Deguchi, K.; Nakano, Y.; Abe, K. Combination therapy of cholinesterase inhibitor (donepezil or galantamine) plus memantine in the Okayama Memantine Study. J. Alzheimers Dis., 2015, 45(3), 771-780.
[http://dx.doi.org/10.3233/JAD-143084] [PMID: 25624417]
[28]
Small, G.W.; Greenfield, S. Current and future treatments for Alzheimer disease. Am. J. Geriatr. Psychiatry, 2015, 23(11), 1101-1105.
[http://dx.doi.org/10.1016/j.jagp.2015.08.006] [PMID: 26614911]
[29]
Yiannopoulou, K.G.; Papageorgiou, S.G. Current and future treatments for Alzheimer’s disease. Ther. Adv. Neurol. Disorder., 2013, 6(1), 19-33.
[http://dx.doi.org/10.1177/1756285612461679] [PMID: 23277790]
[30]
de Oliveira Pedrosa, M.; Duarte da Cruz, R.M.; de Oliveira Viana, J.; de Moura, R.O.; Ishiki, H.M.; Barbosa Filho, J.M.; Diniz, M.F.; Scotti, M.T.; Scotti, L.; Bezerra Mendonca, F.J. Hybrid compounds as direct multitarget ligands: A review. Curr. Top. Med. Chem., 2017, 17(9), 1044-1079.
[http://dx.doi.org/10.2174/1568026616666160927160620] [PMID: 27697048]
[31]
Oset-Gasque, M.J.; Marco-Contelles, J. Alzheimer’s disease, the “one-molecule, one-target” paradigm, and the multitarget directed ligand approach. ACS Chem. Neurosci., 2018, 9(3), 401-403.
[http://dx.doi.org/10.1021/acschemneuro.8b00069] [PMID: 29465220]
[32]
Talesa, V.N. Acetylcholinesterase in Alzheimer’s disease. Mech. Ageing Dev., 2001, 122(16), 1961-1969.
[http://dx.doi.org/10.1016/S0047-6374(01)00309-8] [PMID: 11589914]
[33]
Bartus, R.T.; Dean, R.L., III; Beer, B.; Lippa, A.S. The cholinergic hypothesis of geriatric memory dysfunction. Science, 1982, 217(4558), 408-414.
[http://dx.doi.org/10.1126/science.7046051] [PMID: 7046051]
[34]
Tariot, P.N.; Cohen, R.M.; Sunderland, T.; Newhouse, P.A.; Yount, D.; Mellow, A.M.; Weingartner, H.; Mueller, E.A.; Murphy, D.L. L-deprenyl in Alzheimer’s disease. Preliminary evidence for behavioral change with monoamine oxidase B inhibition. Arch. Gen. Psychiatry, 1987, 44(5), 427-433.
[http://dx.doi.org/10.1001/archpsyc.1987.01800170041007] [PMID: 3107514]
[35]
Avramovich-Tirosh, Y.; Amit, T.; Bar-Am, O.; Zheng, H.; Fridkin, M.; Youdim, M.B. Therapeutic targets and potential of the novel brain- permeable multifunctional iron chelator-monoamine oxidase inhibitor drug, M-30, for the treatment of Alzheimer’s disease. J. Neurochem., 2007, 100(2), 490-502.
[http://dx.doi.org/10.1111/j.1471-4159.2006.04258.x] [PMID: 17144902]
[36]
Hardy, J. Amyloid, the presenilins and Alzheimer’s disease. Trends Neurosci., 1997, 20(4), 154-159.
[http://dx.doi.org/10.1016/S0166-2236(96)01030-2] [PMID: 9106355]
[37]
Hardy, J. Alzheimer’s disease: The amyloid cascade hypothesis: An update and reappraisal. J. Alzheimers Dis., 2006, 9(3)(Suppl.), 151-153.
[http://dx.doi.org/10.3233/JAD-2006-9S317] [PMID: 16914853]
[38]
Hardy, J.; Selkoe, D.J. The amyloid hypothesis of Alzheimer’s disease: Progress and problems on the road to therapeutics. Science, 2002, 297(5580), 353-356.
[http://dx.doi.org/10.1126/science.1072994] [PMID: 12130773]
[39]
Lin, M.T.; Beal, M.F. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature, 2006, 443(7113), 787-795.
[http://dx.doi.org/10.1038/nature05292] [PMID: 17051205]
[40]
Goedert, M.; Spillantini, M.G.; Jakes, R.; Rutherford, D.; Crowther, R.A. Multiple isoforms of human microtubule-associated protein tau: Sequences and localization in neurofibrillary tangles of Alzheimer’s disease. Neuron, 1989, 3(4), 519-526.
[http://dx.doi.org/10.1016/0896-6273(89)90210-9] [PMID: 2484340]
[41]
Zheng, W.; Monnot, A.D. Regulation of brain iron and copper homeostasis by brain barrier systems: Implication in neurodegenerative diseases. Pharmacol. Ther., 2012, 133(2), 177-188.
[http://dx.doi.org/10.1016/j.pharmthera.2011.10.006] [PMID: 22115751]
[42]
Villeneuve, S.; Wirth, M.; La Joie, R. Are AD-typical regions the convergence point of multiple pathologies? Front. Aging Neurosci., 2015, 7, 42.
[http://dx.doi.org/10.3389/fnagi.2015.00042] [PMID: 25859215]
[43]
Wirth, M.; Villeneuve, S.; Haase, C.M.; Madison, C.M.; Oh, H.; Landau, S.M.; Rabinovici, G.D.; Jagust, W.J. Associations between Alzheimer disease biomarkers, neurodegeneration, and cognition in cognitively normal older people. JAMA Neurol., 2013, 70(12), 1512-1519.
[http://dx.doi.org/10.1001/jamaneurol.2013.4013] [PMID: 24166579]
[44]
Villeneuve, S.; Reed, B.R.; Madison, C.M.; Wirth, M.; Marchant, N.L.; Kriger, S.; Mack, W.J.; Sanossian, N.; DeCarli, C.; Chui, H.C.; Weiner, M.W.; Jagust, W.J. Vascular risk and Aβ interact to reduce cortical thickness in AD vulnerable brain regions. Neurology, 2014, 83(1), 40-47.
[http://dx.doi.org/10.1212/WNL.0000000000000550] [PMID: 24907234]
[45]
Lipton, S.A. The molecular basis of memantine action in Alzheimer’s disease and other neurologic disorders: Low-affinity, uncompetitive antagonism. Curr. Alzheimer Res., 2005, 2(2), 155-165.
[http://dx.doi.org/10.2174/1567205053585846] [PMID: 15974913]
[46]
Hooper, C.; Killick, R.; Lovestone, S. The GSK3 hypothesis of Alzheimer’s disease. J. Neurochem., 2008, 104(6), 1433-1439.
[http://dx.doi.org/10.1111/j.1471-4159.2007.05194.x] [PMID: 18088381]
[47]
Pérez-Torres, S.; Cortés, R.; Tolnay, M.; Probst, A.; Palacios, J.M.; Mengod, G. Alterations on phosphodiesterase type 7 and 8 isozyme mRNA expression in Alzheimer’s disease brains examined by in situ hybridization. Exp. Neurol., 2003, 182(2), 322-334.
[http://dx.doi.org/10.1016/S0014-4886(03)00042-6] [PMID: 12895443]
[48]
Bollen, E.; Prickaerts, J. Phosphodiesterases in neurodegenerative disorders. IUBMB Life, 2012, 64(12), 965-970.
[http://dx.doi.org/10.1002/iub.1104] [PMID: 23129425]
[49]
Morawski, M.; Schilling, S.; Kreuzberger, M.; Waniek, A.; Jäger, C.; Koch, B.; Cynis, H.; Kehlen, A.; Arendt, T.; Hartlage-Rübsamen, M.; Demuth, H.U.; Roßner, S. Glutaminyl cyclase in human cortex: Correlation with (pGlu)-amyloid-β load and cognitive decline in Alzheimer’s disease. J. Alzheimers Dis., 2014, 39(2), 385-400.
[http://dx.doi.org/10.3233/JAD-131535] [PMID: 24164736]
[50]
Saido, T.C.; Iwatsubo, T.; Mann, D.M.; Shimada, H.; Ihara, Y.; Kawashima, S. Dominant and differential deposition of distinct β-amyloid peptide species, A β N3(pE), in senile plaques. Neuron, 1995, 14(2), 457-466.
[http://dx.doi.org/10.1016/0896-6273(95)90301-1] [PMID: 7857653]
[51]
Mal, S.; Dwivedi, A.R.; Kumar, V.; Kumar, N.; Kumar, B.; Kumar, V. Role of Peroxisome Proliferated Activated Receptor gamma (PPARγ) in Different Disease States: Recent Updates. Curr. Med. Chem., 2021, 28(16), 3193-3215.
[http://dx.doi.org/10.2174/0929867327666200716113136] [PMID: 32674727]
[52]
Kitamura, Y.; Shimohama, S.; Koike, H.; Kakimura, J-i.; Matsuoka, Y.; Nomura, Y.; Gebicke-Haerter, P.J.; Taniguchi, T. Increased expression of cyclooxygenases and peroxisome proliferator-activated receptor-γ in Alzheimer’s disease brains. Biochem. Biophys. Res. Commun., 1999, 254(3), 582-586.
[http://dx.doi.org/10.1006/bbrc.1998.9981] [PMID: 9920782]
[53]
Sastre, M.; Dewachter, I.; Landreth, G.E.; Willson, T.M.; Klockgether, T.; van Leuven, F.; Heneka, M.T. Nonsteroidal anti-inflammatory drugs and peroxisome proliferator-activated receptor-γ agonists modulate immunostimulated processing of amyloid precursor protein through regulation of β-secretase. J. Neurosci., 2003, 23(30), 9796-9804.
[http://dx.doi.org/10.1523/JNEUROSCI.23-30-09796.2003] [PMID: 14586007]
[54]
Sastre, M.; Roßner, S.; Bogdanovic, N.; Rosen, E.; Dewachter, I.; Borghgraef, P.; Evert, B.; Dumitrescu-Ozimek, L.; Thal, D.; Landreth, G. NSAIDs repress BACE1 gene promoter activity by activation of PPARgamma. Aktuelle Neurologie, 2005, 32(S 4), V66.
[http://dx.doi.org/10.1055/s-2005-919211]
[55]
Camacho, I.E.; Serneels, L.; Spittaels, K.; Merchiers, P.; Dominguez, D.; De Strooper, B. Peroxisome-proliferator-activated receptor γ induces a clearance mechanism for the amyloid-β peptide. J. Neurosci., 2004, 24(48), 10908-10917.
[http://dx.doi.org/10.1523/JNEUROSCI.3987-04.2004] [PMID: 15574741]
[56]
d’Abramo, C.; Massone, S.; Zingg, J-M.; Pizzuti, A.; Marambaud, P.; Dalla Piccola, B.; Azzi, A.; Marinari, U.M.; Pronzato, M.A.; Ricciarelli, R. Role of peroxisome proliferator-activated receptor γ in amyloid precursor protein processing and amyloid β-mediated cell death. Biochem. J., 2005, 391(Pt 3), 693-698.
[http://dx.doi.org/10.1042/BJ20050560] [PMID: 15946122]
[57]
Sanchez-Mejia, R.O.; Newman, J.W.; Toh, S.; Yu, G-Q.; Zhou, Y.; Halabisky, B.; Cissé, M.; Scearce-Levie, K.; Cheng, I.H.; Gan, L.; Palop, J.J.; Bonventre, J.V.; Mucke, L. Phospholipase A2 reduction ameliorates cognitive deficits in a mouse model of Alzheimer’s disease. Nat. Neurosci., 2008, 11(11), 1311-1318.
[http://dx.doi.org/10.1038/nn.2213] [PMID: 18931664]
[58]
Du, H.; Guo, L.; Fang, F.; Chen, D.; Sosunov, A.A.; McKhann, G.M.; Yan, Y.; Wang, C.; Zhang, H.; Molkentin, J.D.; Gunn-Moore, F.J.; Vonsattel, J.P.; Arancio, O.; Chen, J.X.; Yan, S.D. Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer’s disease. Nat. Med., 2008, 14(10), 1097-1105.
[http://dx.doi.org/10.1038/nm.1868] [PMID: 18806802]
[59]
Bernardo, A.; Harrison, F.E.; McCord, M.; Zhao, J.; Bruchey, A.; Davies, S.S.; Jackson Roberts, L., II; Mathews, P.M.; Matsuoka, Y.; Ariga, T.; Yu, R.K.; Thompson, R.; McDonald, M.P. Elimination of GD3 synthase improves memory and reduces amyloid-β plaque load in transgenic mice. Neurobiol. Aging, 2009, 30(11), 1777-1791.
[http://dx.doi.org/10.1016/j.neurobiolaging.2007.12.022] [PMID: 18258340]
[60]
Melchor, J.P.; Pawlak, R.; Strickland, S. The tissue plasminogen activator-plasminogen proteolytic cascade accelerates amyloid-β (Abeta) degradation and inhibits Abeta-induced neurodegeneration. J. Neurosci., 2003, 23(26), 8867-8871.
[http://dx.doi.org/10.1523/JNEUROSCI.23-26-08867.2003] [PMID: 14523088]
[61]
Caricasole, A.; Copani, A.; Caraci, F.; Aronica, E.; Rozemuller, A.J.; Caruso, A.; Storto, M.; Gaviraghi, G.; Terstappen, G.C.; Nicoletti, F. Induction of Dickkopf-1, a negative modulator of the Wnt pathway, is associated with neuronal degeneration in Alzheimer’s brain. J. Neurosci., 2004, 24(26), 6021-6027.
[http://dx.doi.org/10.1523/JNEUROSCI.1381-04.2004] [PMID: 15229249]
[62]
Saito, K.; Elce, J.S.; Hamos, J.E.; Nixon, R.A. Widespread activation of calcium-activated neutral proteinase (calpain) in the brain in Alzheimer disease: A potential molecular basis for neuronal degeneration. Proc. Natl. Acad. Sci. USA, 1993, 90(7), 2628-2632.
[http://dx.doi.org/10.1073/pnas.90.7.2628] [PMID: 8464868]
[63]
Kilgore, M.; Miller, C.A.; Fass, D.M.; Hennig, K.M.; Haggarty, S.J.; Sweatt, J.D.; Rumbaugh, G. Inhibitors of class 1 histone deacetylases reverse contextual memory deficits in a mouse model of Alzheimer’s disease. Neuropsychopharmacology, 2010, 35(4), 870-880.
[http://dx.doi.org/10.1038/npp.2009.197] [PMID: 20010553]
[64]
Gauthier, S. Advances in the pharmacotherapy of Alzheimer’s disease. CMAJ, 2002, 166(5), 616-623.
[PMID: 11898943]
[65]
Pákáski, M.; Kálmán, J. Interactions between the amyloid and cholinergic mechanisms in Alzheimer’s disease. Neurochem. Int., 2008, 53(5), 103-111.
[http://dx.doi.org/10.1016/j.neuint.2008.06.005] [PMID: 18602955]
[66]
Riederer, P.; Danielczyk, W.; Grünblatt, E. Monoamine oxidase-B inhibition in Alzheimer’s disease. Neurotoxicology, 2004, 25(1-2), 271-277.
[http://dx.doi.org/10.1016/S0161-813X(03)00106-2] [PMID: 14697902]
[67]
Selkoe, D.J. Alzheimer’s disease: Genes, proteins, and therapy. Physiol. Rev., 2001, 81(2), 741-766.
[http://dx.doi.org/10.1152/physrev.2001.81.2.741] [PMID: 11274343]
[68]
Vitale, R.M.; Rispoli, V.; Desiderio, D.; Sgammato, R.; Thellung, S.; Canale, C.; Vassalli, M.; Carbone, M.; Ciavatta, M.L.; Mollo, E.; Felicità, V.; Arcone, R.; Gavagnin Capoggiani, M.; Masullo, M.; Florio, T.; Amodeo, P. In Silico identification and experimental validation of novel anti-alzheimer’s multitargeted ligands from a marine source featuring a “2-aminoimidazole plus aromatic group” scaffold. ACS Chem. Neurosci., 2018, 9(6), 1290-1303.
[http://dx.doi.org/10.1021/acschemneuro.7b00416] [PMID: 29473731]
[69]
Wright, C.I.; Geula, C.; Mesulam, M.M. Neurological cholinesterases in the normal brain and in Alzheimer’s disease: Relationship to plaques, tangles, and patterns of selective vulnerability. Ann. Neurol., 1993, 34(3), 373-384.
[http://dx.doi.org/10.1002/ana.410340312] [PMID: 8363355]
[70]
Polinsky, R.J.; Holmes, K.V.; Brown, R.T.; Weise, V. CSF acetylcholinesterase levels are reduced in multiple system atrophy with autonomic failure. Neurology, 1989, 39(1), 40-44.
[http://dx.doi.org/10.1212/WNL.39.1.40] [PMID: 2909912]
[71]
Binda, C.; Newton-Vinson, P.; Hubálek, F.; Edmondson, D.E.; Mattevi, A. Structure of human monoamine oxidase B, a drug target for the treatment of neurological disorders. Nat. Struct. Biol., 2002, 9(1), 22-26.
[http://dx.doi.org/10.1038/nsb732] [PMID: 11753429]
[72]
Youdim, M.B.; Edmondson, D.; Tipton, K.F. The therapeutic potential of monoamine oxidase inhibitors. Nat. Rev. Neurosci., 2006, 7(4), 295-309.
[http://dx.doi.org/10.1038/nrn1883] [PMID: 16552415]
[73]
Shih, J.C.; Thompson, R.F. Monoamine oxidase in neuropsychiatry and behavior. Am. J. Hum. Genet., 1999, 65(3), 593-598.
[http://dx.doi.org/10.1086/302562] [PMID: 10441564]
[74]
Kumar, B.; Gupta, V.P.; Kumar, V. A perspective on monoamine oxidase enzyme as drug target: Challenges and opportunities. Curr. Drug Targets, 2017, 18(1), 87-97.
[http://dx.doi.org/10.2174/1389450117666151209123402] [PMID: 26648064]
[75]
Christen, Y. Oxidative stress and Alzheimer disease. Am. J. Clin. Nutr., 2000, 71(2), 621S-629S.
[http://dx.doi.org/10.1093/ajcn/71.2.621s] [PMID: 10681270]
[76]
Bortolato, M.; Chen, K.; Shih, J.C. Monoamine oxidase inactivation: From pathophysiology to therapeutics. Adv. Drug Deliv. Rev., 2008, 60(13-14), 1527-1533.
[http://dx.doi.org/10.1016/j.addr.2008.06.002] [PMID: 18652859]
[77]
Hardy, J.; Allsop, D. Amyloid deposition as the central event in the aetiology of Alzheimer’s disease. Trends Pharmacol. Sci., 1991, 12(10), 383-388.
[http://dx.doi.org/10.1016/0165-6147(91)90609-V] [PMID: 1763432]
[78]
Walsh, D.M.; Selkoe, D.J. A beta oligomers - a decade of discovery. J. Neurochem., 2007, 101(5), 1172-1184.
[http://dx.doi.org/10.1111/j.1471-4159.2006.04426.x] [PMID: 17286590]
[79]
Swerdlow, R.H. Mitochondria and mitochondrial cascades in Alzheimer’s disease. J. Alzheimers Dis., 2018, 62(3), 1403-1416.
[http://dx.doi.org/10.3233/JAD-170585] [PMID: 29036828]
[80]
Sang, S.; Pan, X.; Chen, Z.; Zeng, F.; Pan, S.; Liu, H.; Jin, L.; Fei, G.; Wang, C.; Ren, S.; Jiao, F.; Bao, W.; Zhou, W.; Guan, Y.; Zhang, Y.; Shi, H.; Wang, Y.; Yu, X.; Wang, Y.; Zhong, C. Thiamine diphosphate reduction strongly correlates with brain glucose hypometabolism in Alzheimer’s disease, whereas amyloid deposition does not. Alzheimers Res. Ther., 2018, 10(1), 26.
[http://dx.doi.org/10.1186/s13195-018-0354-2] [PMID: 29490669]
[81]
Wang, W.; Zhao, F.; Ma, X.; Perry, G.; Zhu, X. Mitochondria dysfunction in the pathogenesis of Alzheimer’s disease: Recent advances. Mol. Neurodegener., 2020, 15(1), 30.
[http://dx.doi.org/10.1186/s13024-020-00376-6] [PMID: 32471464]
[82]
Hroudová, J.; Singh, N.; Fišar, Z.; Ghosh, K.K. Progress in drug development for Alzheimer’s disease: An overview in relation to mitochondrial energy metabolism. Eur. J. Med. Chem., 2016, 121, 774-784.
[http://dx.doi.org/10.1016/j.ejmech.2016.03.084] [PMID: 27094132]
[83]
Ferris, S.H. Evaluation of memantine for the treatment of Alzheimer’s disease. Expert Opin. Pharmacother., 2003, 4(12), 2305-2313.
[http://dx.doi.org/10.1517/14656566.4.12.2305] [PMID: 14640929]
[84]
Kabir, M.T.; Sufian, M.A.; Uddin, M.S.; Begum, M.M.; Akhter, S.; Islam, A.; Mathew, B.; Islam, M.S.; Amran, M.S.; Md Ashraf, G. NMDA receptor antagonists: repositioning of memantine as a multitargeting agent for alzheimer’s therapy. Curr. Pharm. Des., 2019, 25(33), 3506-3518.
[http://dx.doi.org/10.2174/1381612825666191011102444] [PMID: 31604413]
[85]
Brown, D.R.; Kozlowski, H. Biological inorganic and bioinorganic chemistry of neurodegeneration based on prion and Alzheimer diseases. Dalton Trans., 2004, 13(13), 1907-1917.
[http://dx.doi.org/10.1039/b401985g] [PMID: 15252577]
[86]
Hughes, R.E.; Nikolic, K.; Ramsay, R.R. One for all? Hitting multiple Alzheimer’s disease targets with one drug. Front. Neurosci., 2016, 10, 177.
[http://dx.doi.org/10.3389/fnins.2016.00177] [PMID: 27199640]
[87]
Cavalli, A.; Bolognesi, M.L.; Minarini, A.; Rosini, M.; Tumiatti, V.; Recanatini, M.; Melchiorre, C. Multi-target-directed ligands to combat neurodegenerative diseases. J. Med. Chem., 2008, 51(3), 347-372.
[http://dx.doi.org/10.1021/jm7009364] [PMID: 18181565]
[88]
Jalili-Baleh, L.; Babaei, E.; Abdpour, S.; Nasir Abbas Bukhari, S.; Foroumadi, A.; Ramazani, A.; Sharifzadeh, M.; Abdollahi, M.; Khoobi, M. A review on flavonoid-based scaffolds as multi-target-directed ligands (MTDLs) for Alzheimer’s disease. Eur. J. Med. Chem., 2018, 152, 570-589.
[http://dx.doi.org/10.1016/j.ejmech.2018.05.004] [PMID: 29763806]
[89]
Minarini, A.; Milelli, A.; Tumiatti, V.; Rosini, M.; Simoni, E.; Bolognesi, M.L.; Andrisano, V.; Bartolini, M.; Motori, E.; Angeloni, C.; Hrelia, S. Cystamine-tacrine dimer: A new multi-target-directed ligand as potential therapeutic agent for Alzheimer’s disease treatment. Neuropharmacology, 2012, 62(2), 997-1003.
[http://dx.doi.org/10.1016/j.neuropharm.2011.10.007] [PMID: 22032870]
[90]
Lu, X.; He, S.Y.; Li, Q.; Yang, H.; Jiang, X.; Lin, H.; Chen, Y.; Qu, W.; Feng, F.; Bian, Y.; Zhou, Y.; Sun, H. Investigation of multi-target-directed ligands (MTDLs) with butyrylcholinesterase (BuChE) and indoleamine 2,3-dioxygenase 1 (IDO1) inhibition: The design, synthesis of miconazole analogues targeting Alzheimer’s disease. Bioorg. Med. Chem., 2018, 26(8), 1665-1674.
[http://dx.doi.org/10.1016/j.bmc.2018.02.014] [PMID: 29475581]
[91]
Mao, F.; Li, J.; Wei, H.; Huang, L.; Li, X. Tacrine-propargylamine derivatives with improved acetylcholinesterase inhibitory activity and lower hepatotoxicity as a potential lead compound for the treatment of Alzheimer’s disease. J. Enzyme Inhib. Med. Chem., 2015, 30(6), 995-1001.
[http://dx.doi.org/10.3109/14756366.2014.1003212] [PMID: 25792506]
[92]
Xu, Y.X.; Wang, H.; Li, X.K.; Dong, S.N.; Liu, W.W.; Gong, Q.; Wang, T.D.; Tang, Y.; Zhu, J.; Li, J.; Zhang, H.Y.; Mao, F. Discovery of novel propargylamine-modified 4-aminoalkyl imidazole substituted pyrimidinylthiourea derivatives as multifunctional agents for the treatment of Alzheimer’s disease. Eur. J. Med. Chem., 2018, 143, 33-47.
[http://dx.doi.org/10.1016/j.ejmech.2017.08.025] [PMID: 29172081]
[93]
Das, S.; Basu, S. Multi-targeting strategies for Alzheimer’s disease therapeutics: Pros and cons. Curr. Top. Med. Chem., 2017, 17(27), 3017-3061.
[http://dx.doi.org/10.2174/1568026617666170707130652] [PMID: 28685694]
[94]
Batool, A.; Kamal, M.A.; Rizvi, S.M.D.; Rashid, S. Topical discoveries on multi-target approach to manage Alzheimer’s disease. Curr. Drug Metab., 2018, 19(8), 704-713.
[http://dx.doi.org/10.2174/1389200219666180305152553] [PMID: 29512457]
[95]
Wang, N.; Qiu, P.; Cui, W.; Yan, X.; Zhang, B.; He, S. Recent Advances in Multi-target Anti-Alzheimer Disease Compounds (2013 Up to the Present). Curr. Med. Chem., 2019, 26(30), 5684-5710.
[http://dx.doi.org/10.2174/0929867326666181203124102] [PMID: 30501591]
[96]
de Freitas Silva, M.; Dias, K.S.T.; Gontijo, V.S.; Ortiz, C.J.C.; Viegas, C. Jr Multi-target directed drugs as a modern approach for drug design towards Alzheimer’s disease: An update. Curr. Med. Chem., 2018, 25(29), 3491-3525.
[http://dx.doi.org/10.2174/0929867325666180111101843] [PMID: 29332563]
[97]
Bolognesi, M.L.; Minarini, A.; Rosini, M.; Tumiatti, V.; Melchiorre, C. From dual binding site acetylcholinesterase inhibitors to multi-target-directed ligands (MTDLs): A step forward in the treatment of Alzheimer’s disease. Mini Rev. Med. Chem., 2008, 8(10), 960-967.
[http://dx.doi.org/10.2174/138955708785740652] [PMID: 18782050]
[98]
Sameem, B.; Saeedi, M.; Mahdavi, M.; Shafiee, A. A review on tacrine-based scaffolds as multi-target drugs (MTDLs) for Alzheimer’s disease. Eur. J. Med. Chem., 2017, 128, 332-345.
[http://dx.doi.org/10.1016/j.ejmech.2016.10.060] [PMID: 27876467]
[99]
Umar, T.; Hoda, N. Alzheimer’s disease: A systemic review of substantial therapeutic targets and the leading multi-functional molecules. Curr. Top. Med. Chem., 2017, 17(31), 3370-3389.
[http://dx.doi.org/10.2174/1568026618666180112161024] [PMID: 29332579]
[100]
Zhang, X.; He, X.; Chen, Q.; Lu, J.; Rapposelli, S.; Pi, R. A review on the hybrids of hydroxycinnamic acid as multi-target-directed ligands against Alzheimer’s disease. Bioorg. Med. Chem., 2018, 26(3), 543-550.
[http://dx.doi.org/10.1016/j.bmc.2017.12.042] [PMID: 29310862]
[101]
Weinreb, O.; Mandel, S.; Bar-Am, O.; Yogev-Falach, M.; Avramovich-Tirosh, Y.; Amit, T.; Youdim, M.B. Multifunctional neuroprotective derivatives of rasagiline as anti-Alzheimer’s disease drugs. Neurotherapeutics, 2009, 6(1), 163-174.
[http://dx.doi.org/10.1016/j.nurt.2008.10.030] [PMID: 19110207]
[102]
Li, Q.; He, S.; Chen, Y.; Feng, F.; Qu, W.; Sun, H. Donepezil-based multi-functional cholinesterase inhibitors for treatment of Alzheimer’s disease. Eur. J. Med. Chem., 2018, 158, 463-477.
[http://dx.doi.org/10.1016/j.ejmech.2018.09.031] [PMID: 30243151]
[103]
Zhang, P.; Xu, S.; Zhu, Z.; Xu, J. Multi-target design strategies for the improved treatment of Alzheimer’s disease. Eur. J. Med. Chem., 2019, 176, 228-247.
[http://dx.doi.org/10.1016/j.ejmech.2019.05.020] [PMID: 31103902]
[104]
Wang, T.; Liu, X.H.; Guan, J.; Ge, S.; Wu, M-B.; Lin, J.P.; Yang, L.R. Advancement of multi-target drug discoveries and promising applications in the field of Alzheimer’s disease. Eur. J. Med. Chem., 2019, 169, 200-223.
[http://dx.doi.org/10.1016/j.ejmech.2019.02.076] [PMID: 30884327]
[105]
Mathew, B.; Parambi, D.G.T.; Mathew, G.E.; Uddin, M.S.; Inasu, S.T.; Kim, H.; Marathakam, A.; Unnikrishnan, M.K.; Carradori, S. Emerging therapeutic potentials of dual-acting MAO and AChE inhibitors in Alzheimer’s and Parkinson’s diseases. Arch. Pharm. (Weinheim), 2019, 352(11), e1900177.
[http://dx.doi.org/10.1002/ardp.201900177] [PMID: 31478569]
[106]
Yáñez, M.; Viña, D. Dual inhibitors of monoamine oxidase and cholinesterase for the treatment of Alzheimer disease. Curr. Top. Med. Chem., 2013, 13(14), 1692-1706.
[http://dx.doi.org/10.2174/15680266113139990120] [PMID: 23889051]
[107]
Zheng, H.; Amit, T.; Bar-Am, O.; Fridkin, M.; Youdim, M.B.; Mandel, S.A. From anti-Parkinson’s drug rasagiline to novel multitarget iron chelators with acetylcholinesterase and monoamine oxidase inhibitory and neuroprotective properties for Alzheimer’s disease. J. Alzheimers Dis., 2012, 30(1), 1-16.
[http://dx.doi.org/10.3233/JAD-2012-120013] [PMID: 22387411]
[108]
Wang, X-B.; Yin, F-C.; Huang, M.; Jiang, N.; Lan, J-S.; Kong, L-Y. Chromone and donepezil hybrids as new multipotent cholinesterase and monoamine oxidase inhibitors for the potential treatment of Alzheimer’s disease. RSC Med Chem, 2020, 11(2), 225-233.
[http://dx.doi.org/10.1039/C9MD00441F] [PMID: 33479629]
[109]
Yun, Y.; Yang, J.; Miao, Y.; Wang, X.; Sun, J. Synthesis and biological evaluation of 4-arylcoumarins as potential anti-Alzheimer’s disease agents. Bioorg. Med. Chem. Lett., 2020, 30(4), 126900.
[http://dx.doi.org/10.1016/j.bmcl.2019.126900] [PMID: 31882295]
[110]
Tian, C.; Qiang, X.; Song, Q.; Cao, Z.; Ye, C.; He, Y.; Deng, Y.; Zhang, L. Flurbiprofen-chalcone hybrid Mannich base derivatives as balanced multifunctional agents against Alzheimer’s disease: Design, synthesis and biological evaluation. Bioorg. Chem., 2020, 94, 103477.
[http://dx.doi.org/10.1016/j.bioorg.2019.103477] [PMID: 31818478]
[111]
Kumar, B.; Kumar, V.; Prashar, V.; Saini, S.; Dwivedi, A.R.; Bajaj, B.; Mehta, D.; Parkash, J.; Kumar, V. Dipropargyl substituted diphenylpyrimidines as dual inhibitors of monoamine oxidase and acetylcholinesterase. Eur. J. Med. Chem., 2019, 177, 221-234.
[http://dx.doi.org/10.1016/j.ejmech.2019.05.039] [PMID: 31151057]
[112]
Zhang, X.; Song, Q.; Cao, Z.; Li, Y.; Tian, C.; Yang, Z.; Zhang, H.; Deng, Y. Design, synthesis and evaluation of chalcone Mannich base derivatives as multifunctional agents for the potential treatment of Alzheimer’s disease. Bioorg. Chem., 2019, 87, 395-408.
[http://dx.doi.org/10.1016/j.bioorg.2019.03.043] [PMID: 30921741]
[113]
Sang, Z.; Wang, K.; Zhang, P.; Shi, J.; Liu, W.; Tan, Z. Design, synthesis, in-silico and biological evaluation of novel chalcone derivatives as multi-function agents for the treatment of Alzheimer’s disease. Eur. J. Med. Chem., 2019, 180, 238-252.
[http://dx.doi.org/10.1016/j.ejmech.2019.07.021] [PMID: 31310916]
[114]
Bai, P.; Wang, K.; Zhang, P.; Shi, J.; Cheng, X.; Zhang, Q.; Zheng, C.; Cheng, Y.; Yang, J.; Lu, X.; Sang, Z. Development of chalcone-O-alkylamine derivatives as multifunctional agents against Alzheimer’s disease. Eur. J. Med. Chem., 2019, 183, 111737.
[http://dx.doi.org/10.1016/j.ejmech.2019.111737] [PMID: 31581002]
[115]
Sang, Z.; Wang, K.; Shi, J.; Liu, W.; Tan, Z. Design, synthesis, in-silico and biological evaluation of novel chalcone-O-carbamate derivatives as multifunctional agents for the treatment of Alzheimer’s disease. Eur. J. Med. Chem., 2019, 178, 726-739.
[http://dx.doi.org/10.1016/j.ejmech.2019.06.026] [PMID: 31229875]
[116]
Sang, Z.; Wang, K.; Han, X.; Cao, M.; Tan, Z.; Liu, W. Design, synthesis, and evaluation of novel ferulic acid derivatives as multi-target-directed ligands for the treatment of Alzheimer’s disease. ACS Chem. Neurosci., 2019, 10(2), 1008-1024.
[http://dx.doi.org/10.1021/acschemneuro.8b00530] [PMID: 30537804]
[117]
Kumar, B. Sheetal; Mantha, A.K.; Kumar, V. Synthesis, biological evaluation and molecular modeling studies of phenyl-/benzhydrylpiperazine derivatives as potential MAO inhibitors. Bioorg. Chem., 2018, 77, 252-262.
[http://dx.doi.org/10.1016/j.bioorg.2018.01.020] [PMID: 29421700]
[118]
Kumar, B.; Kumar, M.; Dwivedi, A.R.; Kumar, V. Synthesis, Biological Evaluation and Molecular Modeling Studies of Propargyl-Containing 2,4,6-Trisubstituted Pyrimidine Derivatives as Potential Anti-Parkinson Agents. ChemMedChem, 2018, 13(7), 705-712.
[http://dx.doi.org/10.1002/cmdc.201700589] [PMID: 29534334]
[119]
Kumar, B.; Dwivedi, A.R.; Sarkar, B.; Gupta, S.K.; Krishnamurthy, S.; Mantha, A.K.; Parkash, J.; Kumar, V. 4, 6-Diphenylpyrimidine derivatives as dual inhibitors of monoamine oxidase and acetylcholinesterase for the treatment of Alzheimer’s disease. ACS Chem. Neurosci., 2019, 10(1), 252-265.
[http://dx.doi.org/10.1021/acschemneuro.8b00220] [PMID: 30296051]
[120]
Kumar, V.; Kumar, B.; Ranjan Dwivedi, A.; Mehta, D.; Kumar, N.; Bajaj, B.; Arora, T.; Prashar, V.; Parkash, J.; Kumar, V. Design, Synthesis and Evaluation of O‐Pentyne Substituted Diphenylpyrimidines as Monoamine Oxidase and Acetylcholinesterase Inhibitors. ChemistrySelect, 2020, 5(27), 8021-8032.
[http://dx.doi.org/10.1002/slct.202002425]
[121]
Chakravarty, H.; Ju, Y.; Chen, W.H.; Tam, K.Y. Dual targeting of cholinesterase and amyloid beta with pyridinium/isoquinolium derivatives. Drug Dev. Res., 2020, 81(2), 242-255.
[http://dx.doi.org/10.1002/ddr.21631] [PMID: 31837041]
[122]
Castro, A.; Martinez, A. Targeting beta-amyloid pathogenesis through acetylcholinesterase inhibitors. Curr. Pharm. Des., 2006, 12(33), 4377-4387.
[http://dx.doi.org/10.2174/138161206778792985] [PMID: 17105433]
[123]
Jeřábek, J.; Uliassi, E.; Guidotti, L.; Korábečný, J.; Soukup, O.; Sepsova, V.; Hrabinova, M.; Kuča, K.; Bartolini, M.; Peña-Altamira, L.E.; Petralla, S.; Monti, B.; Roberti, M.; Bolognesi, M.L. Tacrine-resveratrol fused hybrids as multi-target-directed ligands against Alzheimer’s disease. Eur. J. Med. Chem., 2017, 127, 250-262.
[http://dx.doi.org/10.1016/j.ejmech.2016.12.048] [PMID: 28064079]
[124]
Yan, J.; Hu, J.; Liu, A.; He, L.; Li, X.; Wei, H. Design, synthesis, and evaluation of multitarget-directed ligands against Alzheimer’s disease based on the fusion of donepezil and curcumin. Bioorg. Med. Chem., 2017, 25(12), 2946-2955.
[http://dx.doi.org/10.1016/j.bmc.2017.02.048] [PMID: 28454848]
[125]
Luo, L.; Song, Q.; Li, Y.; Cao, Z.; Qiang, X.; Tan, Z.; Deng, Y. Design, synthesis and evaluation of phthalide alkyl tertiary amine derivatives as promising acetylcholinesterase inhibitors with high potency and selectivity against Alzheimer’s disease. Bioorg. Med. Chem., 2020, 28(8), 115400.
[http://dx.doi.org/10.1016/j.bmc.2020.115400] [PMID: 32146060]
[126]
Panek, D.; Więckowska, 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(2), 347.
[http://dx.doi.org/10.3390/molecules23020347] [PMID: 29414887]
[127]
Panek, D.; Więckowska, A.; Jończyk, J.; Godyń, J.; Bajda, M.; Wichur, T.; Pasieka, A.; Knez, D.; Pišlar, A.; Korabecny, J.; Soukup, O.; Sepsova, V.; Sabaté, R.; Kos, J.; Gobec, S.; Malawska, B. Design, synthesis, and biological evaluation of 1-benzylamino-2-hydroxyalkyl derivatives as new potential disease-modifying multifunctional anti-Alzheimer’s agents. ACS Chem. Neurosci., 2018, 9(5), 1074-1094.
[http://dx.doi.org/10.1021/acschemneuro.7b00461] [PMID: 29345897]
[128]
Chalupova, K.; Korabecny, J.; Bartolini, M.; Monti, B.; Lamba, D.; Caliandro, R.; Pesaresi, A.; Brazzolotto, X.; Gastellier, A-J.; Nachon, F.; Pejchal, J.; Jarosova, M.; Hepnarova, V.; Jun, D.; Hrabinova, M.; Dolezal, R.; Zdarova Karasova, J.; Mzik, M.; Kristofikova, Z.; Misik, J.; Muckova, L.; Jost, P.; Soukup, O.; Benkova, M.; Setnicka, V.; Habartova, L.; Chvojkova, M.; Kleteckova, L.; Vales, K.; Mezeiova, E.; Uliassi, E.; Valis, M.; Nepovimova, E.; Bolognesi, M.L.; Kuca, K. Novel tacrine-tryptophan hybrids: Multi-target directed ligands as potential treatment for Alzheimer’s disease. Eur. J. Med. Chem., 2019, 168, 491-514.
[http://dx.doi.org/10.1016/j.ejmech.2019.02.021] [PMID: 30851693]
[129]
Sang, Z.; Wang, K.; Shi, J.; Liu, W.; Cheng, X.; Zhu, G.; Wang, Y.; Zhao, Y.; Qiao, Z.; Wu, A.; Tan, Z. The development of advanced structural framework as multi-target-directed ligands for the treatment of Alzheimer’s disease. Eur. J. Med. Chem., 2020, 192, 112180.
[http://dx.doi.org/10.1016/j.ejmech.2020.112180] [PMID: 32131034]
[130]
Liu, H.; Qiang, X.; Song, Q.; Li, W.; He, Y.; Ye, C.; Tan, Z.; Deng, Y. Discovery of 4¢-OH-flurbiprofen Mannich base derivatives as potential Alzheimer’s disease treatment with multiple inhibitory activities. Bioorg. Med. Chem., 2019, 27(6), 991-1001.
[http://dx.doi.org/10.1016/j.bmc.2019.01.040] [PMID: 30772129]
[131]
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, 89, 103006.
[http://dx.doi.org/10.1016/j.bioorg.2019.103006] [PMID: 31158577]
[132]
Hiremathad, A.; Keri, R.S.; Esteves, A.R.; Cardoso, S.M.; Chaves, S.; Santos, M.A. Novel Tacrine-Hydroxyphenylbenzimidazole hybrids as potential multitarget drug candidates for Alzheimer’s disease. Eur. J. Med. Chem., 2018, 148, 255-267.
[http://dx.doi.org/10.1016/j.ejmech.2018.02.023] [PMID: 29466775]
[133]
Lanctôt, K.L.; Herrmann, N.; Mazzotta, P. Role of serotonin in the behavioral and psychological symptoms of dementia. J. Neuropsychiatry Clin. Neurosci., 2001, 13(1), 5-21.
[http://dx.doi.org/10.1176/jnp.13.1.5] [PMID: 11207325]
[134]
Buhot, M-C.; Martin, S.; Segu, L. Role of serotonin in memory impairment. Ann. Med., 2000, 32(3), 210-221.
[http://dx.doi.org/10.3109/07853890008998828] [PMID: 10821328]
[135]
Kogen, H.; Toda, N.; Tago, K.; Marumoto, S.; Takami, K.; Ori, M.; Yamada, N.; Koyama, K.; Naruto, S.; Abe, K.; Yamazaki, R.; Hara, T.; Aoyagi, A.; Abe, Y.; Kaneko, T. Design and synthesis of dual inhibitors of acetylcholinesterase and serotonin transporter targeting potential agents for Alzheimer’s disease. Org. Lett., 2002, 4(20), 3359-3362.
[http://dx.doi.org/10.1021/ol026418e] [PMID: 12323018]
[136]
Więckowska, A.; Kołaczkowski, M.; Bucki, A.; Godyń, J.; Marcinkowska, M.; Więckowski, K.; Zaręba, P.; Siwek, A.; Kazek, G.; Głuch-Lutwin, M.; Mierzejewski, P.; Bienkowski, P.; Sienkiewicz-Jarosz, H.; Knez, D.; Wichur, T.; Gobec, S.; Malawska, B. 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., 2016, 124, 63-81.
[http://dx.doi.org/10.1016/j.ejmech.2016.08.016] [PMID: 27560283]
[137]
Więckowska, A.; Wichur, T.; Godyń, J.; Bucki, A.; Marcinkowska, M.; Siwek, A.; Więckowski, K.; Zaręba, P.; Knez, D.; Głuch-Lutwin, M.; Kazek, G.; Latacz, G.; Mika, K.; Kołaczkowski, M.; Korabecny, J.; Soukup, O.; Benkova, M.; Kieć-Kononowicz, K.; Gobec, S.; Malawska, B. Novel multitarget-directed ligands aiming at symptoms and causes of Alzheimer’s disease. ACS Chem. Neurosci., 2018, 9(5), 1195-1214.
[http://dx.doi.org/10.1021/acschemneuro.8b00024] [PMID: 29384656]
[138]
Li, X.; Wang, H.; Xu, Y.; Liu, W.; Gong, Q.; Wang, W.; Qiu, X.; Zhu, J.; Mao, F.; Zhang, H.; Li, J. Novel Vilazodone-Tacrine Hybrids as Potential Multitarget-Directed Ligands for the Treatment of Alzheimer’s Disease Accompanied with Depression: Design, Synthesis, and Biological Evaluation. ACS Chem. Neurosci., 2017, 8(12), 2708-2721.
[http://dx.doi.org/10.1021/acschemneuro.7b00259] [PMID: 28872831]
[139]
Kumar, D.; Sharma, S.; Kalra, S.; Singh, G.; Monga, V.; Kumar, B. Medicinal Perspective of Indole Derivatives: Recent Developments and Structure-Activity Relationship Studies. Curr. Drug Targets, 2020, 21(9), 864-891.
[http://dx.doi.org/10.2174/1389450121666200310115327] [PMID: 32156235]
[140]
Bautista-Aguilera, O.M.; Budni, J.; Mina, F.; Medeiros, E.B.; Deuther-Conrad, W.; Entrena, J.M.; Moraleda, I.; Iriepa, I.; López-Muñoz, F.; Marco-Contelles, J. Contilisant, a tetratarget small molecule for Alzheimer’s disease therapy combining cholinesterase, monoamine oxidase inhibition, and H3R antagonism with S1R agonism profile. J. Med. Chem., 2018, 61(15), 6937-6943.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00848] [PMID: 29969030]
[141]
Bautista-Aguilera, Ó.M.; Hagenow, S.; Palomino-Antolin, A.; Farré-Alins, V.; Ismaili, L.; Joffrin, P.L.; Jimeno, M.L.; Soukup, O.; Janočková, J.; Kalinowsky, L.; Proschak, E.; Iriepa, I.; Moraleda, I.; Schwed, J.S.; Romero Martínez, A.; López-Muñoz, F.; Chioua, M.; Egea, J.; Ramsay, R.R.; Marco-Contelles, J.; Stark, H. Multitarget‐directed ligands combining cholinesterase and monoamine oxidase inhibition with histamine H3R antagonism for neurodegenerative diseases. Angew. Chem. Int. Ed. Engl., 2017, 56(41), 12765-12769.
[http://dx.doi.org/10.1002/anie.201706072] [PMID: 28861918]
[142]
Lalut, J.; Payan, H.; Davis, A.; Lecoutey, C.; Legay, R.; Sopkova-de Oliveira Santos, J.; Claeysen, S.; Dallemagne, P.; Rochais, C. Rational design of novel benzisoxazole derivatives with acetylcholinesterase inhibitory and serotoninergic 5-HT 4 receptors activities for the treatment of Alzheimer’s disease. Sci. Rep., 2020, 10(1), 1-11.
[http://dx.doi.org/10.1038/s41598-020-59805-7] [PMID: 31913322]
[143]
Lecoutey, C.; Rochais, C.; Genest, D.; Butt-Gueulle, S.; Ballandonne, C.; Corvaisier, S.; Dulin, F.; Lepailleur, A.; Sopkova-de Oliveira Santos, J.; Dallemagne, P. Synthesis of dual AChE/5-HT 4 receptor multi-target directed ligands. MedChemComm, 2012, 3(5), 627-634.
[http://dx.doi.org/10.1039/c2md20063e]
[144]
Lecoutey, C.; Hedou, D.; Freret, T.; Giannoni, P.; Gaven, F.; Since, M.; Bouet, V.; Ballandonne, C.; Corvaisier, S.; Malzert Fréon, A.; Mignani, S.; Cresteil, T.; Boulouard, M.; Claeysen, S.; Rochais, C.; Dallemagne, P. Design of donecopride, a dual serotonin subtype 4 receptor agonist/acetylcholinesterase inhibitor with potential interest for Alzheimer’s disease treatment. Proc. Natl. Acad. Sci. USA, 2014, 111(36), E3825-E3830.
[http://dx.doi.org/10.1073/pnas.1410315111] [PMID: 25157130]
[145]
Hatat, B.; Yahiaoui, S.; Lecoutey, C.; Davis, A.; Freret, T.; Boulouard, M.; Claeysen, S.; Rochais, C.; Dallemagne, P. A novel in vivo antiamnesic agent, specially designed to express both acetylcholinesterase (AChE) inhibitory, serotonergic subtype 4 receptor (5-HT4R) agonist and serotonergic subtype 6 receptor (5-HT6R) inverse agonist activities, with a potential interest against Alzheimer’s disease. Front. Aging Neurosci., 2019, 11, 148.
[http://dx.doi.org/10.3389/fnagi.2019.00148] [PMID: 31316368]
[146]
Reyes, A.E.; Perez, D.R.; Alvarez, A.; Garrido, J.; Gentry, M.K.; Doctor, B.P.; Inestrosa, N.C. A monoclonal antibody against acetylcholinesterase inhibits the formation of amyloid fibrils induced by the enzyme. Biochem. Biophys. Res. Commun., 1997, 232(3), 652-655.
[http://dx.doi.org/10.1006/bbrc.1997.6357] [PMID: 9126330]
[147]
Inestrosa, N.C.; Alvarez, A.; Pérez, C.A.; Moreno, R.D.; Vicente, M.; Linker, C.; Casanueva, O.I.; Soto, C.; Garrido, J. Acetylcholinesterase accelerates assembly of amyloid-β-peptides into Alzheimer’s fibrils: Possible role of the peripheral site of the enzyme. Neuron, 1996, 16(4), 881-891.
[http://dx.doi.org/10.1016/S0896-6273(00)80108-7] [PMID: 8608006]
[148]
Cao, Z.; Yang, J.; Xu, R.; Song, Q.; Zhang, X.; Liu, H.; Qiang, X.; Li, Y.; Tan, Z.; Deng, Y. Design, synthesis and evaluation of 4¢-OH-flurbiprofen-chalcone hybrids as potential multifunctional agents for Alzheimer’s disease treatment. Bioorg. Med. Chem., 2018, 26(5), 1102-1115.
[http://dx.doi.org/10.1016/j.bmc.2018.01.030] [PMID: 29409707]
[149]
Nie, Q.; Du, X.G.; Geng, M.Y. Small molecule inhibitors of amyloid β peptide aggregation as a potential therapeutic strategy for Alzheimer’s disease. Acta Pharmacol. Sin., 2011, 32(5), 545-551.
[http://dx.doi.org/10.1038/aps.2011.14] [PMID: 21499284]
[150]
Crescenzi, O.; Tomaselli, S.; Guerrini, R.; Salvadori, S.; D’Ursi, A.M.; Temussi, P.A.; Picone, D. Solution structure of the Alzheimer amyloid β-peptide (1-42) in an apolar microenvironment. Similarity with a virus fusion domain. Eur. J. Biochem., 2002, 269(22), 5642-5648.
[http://dx.doi.org/10.1046/j.1432-1033.2002.03271.x] [PMID: 12423364]
[151]
Yang, Z.; Song, Q.; Cao, Z.; Yu, G.; Liu, Z.; Tan, Z.; Deng, Y. Design, synthesis and evaluation of flurbiprofen-clioquinol hybrids as multitarget-directed ligands against Alzheimer’s disease. Bioorg. Med. Chem., 2020, 28(7), 115374.
[http://dx.doi.org/10.1016/j.bmc.2020.115374] [PMID: 32089390]
[152]
Planel, E.; Sun, X.; Takashima, A. Role of GSK‐3β in Alzheimer’s disease pathology. Drug Dev. Res., 2002, 56(3), 491-510.
[http://dx.doi.org/10.1002/ddr.10100]
[153]
Martinez, A.; Castro, A.; Dorronsoro, I.; Alonso, M. Glycogen synthase kinase 3 (GSK-3) inhibitors as new promising drugs for diabetes, neurodegeneration, cancer, and inflammation. Med. Res. Rev., 2002, 22(4), 373-384.
[http://dx.doi.org/10.1002/med.10011] [PMID: 12111750]
[154]
Jiang, X-Y.; Chen, T-K.; Zhou, J-T.; He, S-Y.; Yang, H-Y.; Chen, Y.; Qu, W.; Feng, F.; Sun, H-P. Dual GSK-3β/AChE inhibitors as a new strategy for multitargeting anti-Alzheimer’s disease drug discovery. ACS Med. Chem. Lett., 2018, 9(3), 171-176.
[http://dx.doi.org/10.1021/acsmedchemlett.7b00463] [PMID: 29541355]
[155]
Oukoloff, K.; Coquelle, N.; Bartolini, M.; Naldi, M.; Le Guével, 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.
[http://dx.doi.org/10.1016/j.ejmech.2018.12.063] [PMID: 30798053]
[156]
Xu, K.; Dai, X.-L.; Huang, H.-C.; Jiang, Z.-F. Targeting HDACs: A promising therapy for Alzheimer's disease. Oxid Med. Cell Longev, 2011, 2011
[http://dx.doi.org/10.1155/2011/143269]
[157]
Yang, S.S.; Zhang, R.; Wang, G.; Zhang, Y.F. The development prospection of HDAC inhibitors as a potential therapeutic direction in Alzheimer’s disease. Transl. Neurodegener., 2017, 6(1), 19.
[http://dx.doi.org/10.1186/s40035-017-0089-1] [PMID: 28702178]
[158]
Xu, A.; He, F.; Zhang, X.; Li, X.; Ran, Y.; Wei, C.; James Chou, C.; Zhang, R.; Wu, J. Tacrine-hydroxamate derivatives as multitarget-directed ligands for the treatment of Alzheimer’s disease: Design, synthesis, and biological evaluation. Bioorg. Chem., 2020, 98, 103721.
[http://dx.doi.org/10.1016/j.bioorg.2020.103721] [PMID: 32193030]
[159]
Tseng, H-J.; Lin, M-H.; Shiao, Y-J.; Yang, Y-C.; Chu, J-C.; Chen, C-Y.; Chen, Y-Y.; Lin, T.E.; Su, C-J.; Pan, S-L.; Chen, L.C.; Wang, C.Y.; Hsu, K.C.; Huang, W.J. Synthesis and biological evaluation of acridine-based histone deacetylase inhibitors as multitarget agents against Alzheimer’s disease. Eur. J. Med. Chem., 2020, 192, 112193.
[http://dx.doi.org/10.1016/j.ejmech.2020.112193] [PMID: 32151835]
[160]
Zhu, F.; Wu, F.; Ma, Y.; Liu, G.; Li, Z.; Sun, Y.; Pei, Z. Decrease in the production of β-amyloid by berberine inhibition of the expression of β-secretase in HEK293 cells. BMC Neurosci., 2011, 12(1), 125.
[http://dx.doi.org/10.1186/1471-2202-12-125] [PMID: 22152059]
[161]
Vassar, R. β-secretase (BACE) as a drug target for Alzheimer’s disease. Adv. Drug Deliv. Rev., 2002, 54(12), 1589-1602.
[http://dx.doi.org/10.1016/S0169-409X(02)00157-6] [PMID: 12453676]
[162]
Vassar, R.; Kovacs, D.M.; Yan, R.; Wong, P.C. The β-secretase enzyme BACE in health and Alzheimer’s disease: Regulation, cell biology, function, and therapeutic potential. J. Neurosci., 2009, 29(41), 12787-12794.
[http://dx.doi.org/10.1523/JNEUROSCI.3657-09.2009] [PMID: 19828790]
[163]
Sharma, P.; Tripathi, A.; Tripathi, P.N.; Singh, S.S.; Singh, S.P.; Shrivastava, S.K. Novel Molecular Hybrids of N-Benzylpiperidine and 1,3,4-Oxadiazole as Multitargeted Therapeutics to Treat Alzheimer’s Disease. ACS Chem. Neurosci., 2019, 10(10), 4361-4384.
[http://dx.doi.org/10.1021/acschemneuro.9b00430] [PMID: 31491074]
[164]
Tripathi, A.; Choubey, P.K.; Sharma, P.; Seth, A.; Tripathi, P.N.; Tripathi, M.K.; Prajapati, S.K.; Krishnamurthy, S.; Shrivastava, S.K. Design and development of molecular hybrids of 2-pyridylpiperazine and 5-phenyl-1,3,4-oxadiazoles as potential multifunctional agents to treat Alzheimer’s disease. Eur. J. Med. Chem., 2019, 183, 111707.
[http://dx.doi.org/10.1016/j.ejmech.2019.111707] [PMID: 31561043]
[165]
Mishra, P.; Sharma, P.; Tripathi, P.N.; Gupta, S.K.; Srivastava, P.; Seth, A.; Tripathi, A.; Krishnamurthy, S.; Shrivastava, S.K. Design and development of 1,3,4-oxadiazole derivatives as potential inhibitors of acetylcholinesterase to ameliorate scopolamine-induced cognitive dysfunctions. Bioorg. Chem., 2019, 89, 103025.
[http://dx.doi.org/10.1016/j.bioorg.2019.103025] [PMID: 31176239]
[166]
Tripathi, A.; Choubey, P.K.; Sharma, P.; Seth, A.; Saraf, P.; Shrivastava, S.K. Design, synthesis, and biological evaluation of ferulic acid based 1,3,4-oxadiazole hybrids as multifunctional therapeutics for the treatment of Alzheimer’s disease. Bioorg. Chem., 2020, 95, 103506.
[http://dx.doi.org/10.1016/j.bioorg.2019.103506] [PMID: 31887472]
[167]
Mahdavi, M.; Saeedi, M.; Gholamnia, L.; Jeddi, S.A.B.; Sabourian, R.; Shafiee, A.; Foroumadi, A.; Akbarzadeh, T. Synthesis of novel tacrine analogs as acetylcholinesterase inhibitors. J. Heterocycl. Chem., 2017, 54(1), 384-390.
[http://dx.doi.org/10.1002/jhet.2594]
[168]
Mahdavi, M.; Hariri, R.; Mirfazli, S.S.; Lotfian, H.; Rastergari, A.; Firuzi, O.; Edraki, N.; Larijani, B.; Akbarzadeh, T.; Saeedi, M. Synthesis and Biological Activity of Some Benzochromenoquinolinones: Tacrine Analogs as Potent Anti-Alzheimer’s Agents. Chem. Biodivers., 2019, 16(4), e1800488.
[http://dx.doi.org/10.1002/cbdv.201800488] [PMID: 30720917]
[169]
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.
[http://dx.doi.org/10.1016/j.bioorg.2018.06.031] [PMID: 29966870]
[170]
Cummings, J.; Lee, G.; Ritter, A.; Sabbagh, M.; Zhong, K. Alzheimer’s disease drug development pipeline: 2019. Alzheimers Dement. (N. Y.), 2019, 5, 272-293.
[http://dx.doi.org/10.1016/j.trci.2019.05.008] [PMID: 31334330]
[171]
Hebron, M.L.; Lonskaya, I.; Olopade, P.; Selby, S.T.; Pagan, F.; Moussa, C.E. Tyrosine kinase inhibition regulates early systemic immune changes and modulates the neuroimmune response in α-synucleinopathy. J. Clin. Cell. Immunol., 2014, 5, 259.
[http://dx.doi.org/10.4172/2155-9899.1000259] [PMID: 25635231]
[172]
Hebron, M.L.; Lonskaya, I.; Moussa, C.E-H. Nilotinib reverses loss of dopamine neurons and improves motor behavior via autophagic degradation of α-synuclein in Parkinson’s disease models. Hum. Mol. Genet., 2013, 22(16), 3315-3328.
[http://dx.doi.org/10.1093/hmg/ddt192] [PMID: 23666528]
[173]
Moussa, C.; Hebron, M.; Li, X.; Xu, H.; Valadez, E.; Yasar, T-Y.; Rogers, S.; Falconer, D.; Mills, R.; Pagan, F. 2016 International Congress, 2016.
[174]
Pagan, F.; Hebron, M.; Valadez, E.H.; Torres-Yaghi, Y.; Huang, X.; Mills, R.R.; Wilmarth, B.M.; Howard, H.; Dunn, C.; Carlson, A.; Lawler, A.; Rogers, S.L.; Falconer, R.A.; Ahn, J.; Li, Z.; Moussa, C. Nilotinib effects in Parkinson’s disease and dementia with Lewy bodies. J. Parkinsons Dis., 2016, 6(3), 503-517.
[http://dx.doi.org/10.3233/JPD-160867] [PMID: 27434297]
[175]
Wang, L.; Wang, R.; Jin, M.; Huang, Y.; Liu, A.; Qin, J.; Chen, M.; Wen, S.; Pi, R.; Shen, W. Carvedilol attenuates 6-hydroxydopamine-induced cell death in PC12 cells: Involvement of Akt and Nrf2/ARE pathways. Neurochem. Res., 2014, 39(9), 1733-1740.
[http://dx.doi.org/10.1007/s11064-014-1367-2] [PMID: 24952068]
[176]
Wang, J.; Ono, K.; Dickstein, D.L.; Arrieta-Cruz, I.; Zhao, W.; Qian, X.; Lamparello, A.; Subnani, R.; Ferruzzi, M.; Pavlides, C.; Ho, L.; Hof, P.R.; Teplow, D.B.; Pasinetti, G.M. Carvedilol as a potential novel agent for the treatment of Alzheimer’s disease. Neurobiol. Aging, 2011, 32(12), 2321.e1-2321.e12.
[http://dx.doi.org/10.1016/j.neurobiolaging.2010.05.004] [PMID: 20579773]
[177]
Grundman, M.; Morgan, R.; Lickliter, J.D.; Schneider, L.S.; DeKosky, S.; Izzo, N.J.; Guttendorf, R.; Higgin, M.; Pribyl, J.; Mozzoni, K.; Safferstein, H.; Catalano, S.M. A phase 1 clinical trial of the sigma-2 receptor complex allosteric antagonist CT1812, a novel therapeutic candidate for Alzheimer’s disease. Alzheimers Dement. (N. Y.), 2019, 5, 20-26.
[http://dx.doi.org/10.1016/j.trci.2018.11.001] [PMID: 30723776]
[178]
Lahmy, V.; Meunier, J.; Malmström, S.; Naert, G.; Givalois, L.; Kim, S.H.; Villard, V.; Vamvakides, A.; Maurice, T. Blockade of Tau hyperphosphorylation and Aβ1−42 generation by the aminotetrahydrofuran derivative ANAVEX2-73, a mixed muscarinic and σ1 receptor agonist, in a nontransgenic mouse model of Alzheimer’s disease. Neuropsychopharmacology, 2013, 38(9), 1706-1723.
[http://dx.doi.org/10.1038/npp.2013.70] [PMID: 23493042]
[179]
Lahmy, V.; Long, R.; Morin, D.; Villard, V.; Maurice, T. Mitochondrial protection by the mixed muscarinic/σ1 ligand ANAVEX2-73, a tetrahydrofuran derivative, in Aβ25-35 peptide-injected mice, a nontransgenic Alzheimer’s disease model. Front. Cell. Neurosci., 2015, 8, 463.
[http://dx.doi.org/10.3389/fncel.2014.00463] [PMID: 25653589]
[180]
Villard, V.; Espallergues, J.; Keller, E.; Vamvakides, A.; Maurice, T. Anti-amnesic and neuroprotective potentials of the mixed muscarinic receptor/sigma 1 (σ1) ligand ANAVEX2-73, a novel aminotetrahydrofuran derivative. J. Psychopharmacol., 2011, 25(8), 1101-1117.
[http://dx.doi.org/10.1177/0269881110379286] [PMID: 20829307]
[181]
Prasanthi, J.R.; Schrag, M.; Dasari, B.; Marwarha, G.; Dickson, A.; Kirsch, W.M.; Ghribi, O. Deferiprone reduces amyloid-β and tau phosphorylation levels but not reactive oxygen species generation in hippocampus of rabbits fed a cholesterol-enriched diet. J. Alzheimers Dis., 2012, 30(1), 167-182.
[http://dx.doi.org/10.3233/JAD-2012-111346] [PMID: 22406440]
[182]
Molina-Holgado, F.; Gaeta, A.; Francis, P.T.; Williams, R.J.; Hider, R.C. Neuroprotective actions of deferiprone in cultured cortical neurones and SHSY-5Y cells. J. Neurochem., 2008, 105(6), 2466-2476.
[http://dx.doi.org/10.1111/j.1471-4159.2008.05332.x] [PMID: 18331585]
[183]
Youdim, M.B. The path from anti Parkinson drug selegiline and rasagiline to multifunctional neuroprotective anti Alzheimer drugs ladostigil and m30. Curr. Alzheimer Res., 2006, 3(5), 541-550.
[http://dx.doi.org/10.2174/156720506779025288] [PMID: 17168653]
[184]
Xiao, S.; Zhang, Z.; Geng, M. Phase 3 Clinical Trial of a Novel and Multi-targeted Oligosaccharide in Patients with Mildmoderate AD in China GV-971 Study Group 2018.
[185]
Burstein, A.H.; Sabbagh, M.; Andrews, R.; Valcarce, C.; Dunn, I.; Altstiel, L. Development of Azeliragon, an oral small molecule antagonist of the receptor for advanced glycation endproducts, for the potential slowing of loss of cognition in mild Alzheimer’s disease. J. Prev. Alzheimers Dis., 2018, 5(2), 149-154.
[PMID: 29616709]
[186]
Satlin, A.; Vanover, K.; Glass, S.; Saillard, J.; Mates, S.; Weingart, M.; Davis, R.E. ITI-007 (Lumateperone) for the treatment of agitation in patients with dementia, including alzheimer’s disease. Alzheimers Dement, 2018, 14(7), 678-P 679.
[http://dx.doi.org/ 10.1016/j.jalz.2018.06.716]

Rights & Permissions Print Cite
Article Metrics
37
1
© 2024 Bentham Science Publishers | Privacy Policy