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Mini-Reviews in Medicinal Chemistry

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ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

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Mini-Review Article

Recent Developments in Tacrine-based Hybrids as a Therapeutic Option for Alzheimer’s Disease

Author(s): Cem Yamali* and Seyda Donmez

Volume 23, Issue 7, 2023

Published on: 19 December, 2022

Page: [869 - 880] Pages: 12

DOI: 10.2174/1389557523666221201145141

Price: $65

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Abstract

Alzheimer's disease (AD) is a multifactorial, irreversible, and age-related neurodegenerative disorder among the elderly. AD attracts attention due to its complex pathogenesis, morbidity and mortality rates, and the limitations of drugs used in the treatment of AD. Cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists are used in the clinic. While tacrine, donepezil, galantamine, and rivastigmine are cholinesterase inhibitors, memantine is a non-competitive NMDA receptor antagonist. However, these drugs could not delay the progress of AD. The traditional clinical approach which is the one drug-one target concept is not entirely effective in the treatment of AD. Also, it is of high-priority to develop potent and novel anti-AD drugs by the design concept of multitarget directed ligands (MTDLs) which combine pharmacophores interacting with different pathways in AD. This article provides an overview of the noteworthy structural modifications made to tacrine to develop novel candidates for anti-Alzheimer drugs. Due to the complex pathology of AD, multifunctional tacrine-based ligands targeting different hallmarks, β-amyloid, tau protein, N-methyl-Daspartate receptor, cholinesterases, monoamine oxidases, secretases, have been studied. Here, tacrinebased derivatives including heterocyclic structures such as dihydroxypyridine, chromene, coumarin, pyrazole, triazole, tetrahydroquinolone, dipicolylamine, arylisoxazole were reported with promising anti-AD effects compared to tacrine. In vitro and in vivo assays showed that new tacrine-based hybrids, which are selective, neuroprotective, and non-hepatotoxic, might be considered as remarkable anti-AD drug candidates for further clinical studies.

Keywords: Alzheimer's disease, tacrine, multi-target directed ligands, MTDLs, β-amyloid, butyrylcholinesterase, acetylcholinesterase.

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[1]
Mangialasche, F.; Solomon, A.; Winblad, B.; Mecocci, P.; Kivipelto, M. Alzheimer’s disease: Clinical trials and drug development. Lancet Neurol., 2010, 9(7), 702-716.
[http://dx.doi.org/10.1016/S1474-4422(10)70119-8] [PMID: 20610346]
[2]
Marešová, P.; Mohelská, H.; Dolejš, J. Kuča, K. Socio-economic aspects of Alzheimer’s disease. Curr. Alzheimer Res., 2015, 12(9), 903-911.
[http://dx.doi.org/10.2174/156720501209151019111448] [PMID: 26510983]
[3]
Cummings, J.; Lee, G.; Nahed, P.; Kambar, M.E.Z.N.; Zhong, K.; Fonseca, J.; Taghva, K. Alzheimer’s disease drug development pipeline: 2022. Alzheimers Dement., 2022, 8(1), e12295.
[http://dx.doi.org/10.1002/trc2.12295] [PMID: 35516416]
[4]
Dementia statistics, Alzheimer’s disease International. 2022. Available from: https://www.alzint.org/about/dementia-facts-figures/dementia-statistics/ (Accessed on: 18 Sept, 2022).
[5]
2021 Alzheimer’s disease facts and figures. Alzheimers Dement., 2021, 17(3), 327-406.
[http://dx.doi.org/10.1002/alz.12328] [PMID: 33756057]
[6]
Fleischman, D.A.; Gabrieli, J. Long-term memory in Alzheimer’s disease. Curr. Opin. Neurobiol., 1999, 9(2), 240-244.
[http://dx.doi.org/10.1016/S0959-4388(99)80034-8] [PMID: 10322182]
[7]
Morris, J.C.; Storandt, M.; Miller, J.P.; McKeel, D.W.; Price, J.L.; Rubin, E.H.; Berg, L. Mild cognitive impairment represents early-stage Alzheimer disease. Arch. Neurol., 2001, 58(3), 397-405.
[http://dx.doi.org/10.1001/archneur.58.3.397] [PMID: 11255443]
[8]
Perry, R.J.; Watson, P.; Hodges, J.R. The nature and staging of attention dysfunction in early (minimal and mild) Alzheimer’s disease: Relationship to episodic and semantic memory impairment. Neuropsychologia, 2000, 38(3), 252-271.
[http://dx.doi.org/10.1016/S0028-3932(99)00079-2] [PMID: 10678692]
[9]
Raji, C.A.; Lopez, O.L.; Kuller, L.H.; Carmichael, O.T.; Becker, J.T. Age, Alzheimer disease, and brain structure. Neurology, 2009, 73(22), 1899-1905.
[http://dx.doi.org/10.1212/WNL.0b013e3181c3f293] [PMID: 19846828]
[10]
Tarawneh, R.; Holtzman, D.M. The clinical problem of symptomatic Alzheimer disease and mild cognitive impairment. Cold Spring Harb. Perspect. Med., 2012, 2(5), a006148.
[http://dx.doi.org/10.1101/cshperspect.a006148] [PMID: 22553492]
[11]
A. Armstrong, R. Risk factors for Alzheimer’s disease. Folia Neuropathol., 2019, 57(2), 87-105.
[http://dx.doi.org/10.5114/fn.2019.85929] [PMID: 31556570]
[12]
Silva, M.V.F.; Loures, C.M.G.; Alves, L.C.V.; de Souza, L.C.; Borges, K.B.G.; Carvalho, M.G. Alzheimer’s disease: Risk factors and potentially protective measures. J. Biomed. Sci., 2019, 26(1), 33.
[http://dx.doi.org/10.1186/s12929-019-0524-y] [PMID: 31072403]
[13]
Takeda, S. Progression of Alzheimer’s disease, tau propagation, and its modifiable risk factors. Neurosci. Res., 2019, 141, 36-42.
[http://dx.doi.org/10.1016/j.neures.2018.08.005] [PMID: 30120962]
[14]
Tiwari, S.; Atluri, V.; Kaushik, A.; Yndart, A.; Nair, M. Alzheimer’s disease: Pathogenesis, diagnostics, and therapeutics. Int. J. Nanomedicine, 2019, 14, 5541-5554.
[http://dx.doi.org/10.2147/IJN.S200490] [PMID: 31410002]
[15]
Alasmari, F.; Alshammari, M.A.; Alasmari, A.F.; Alanazi, W.A.; Alhazzani, K. Neuroinflammatory cytokines induce amyloid beta neurotoxicity through modulating amyloid precursor protein levels/metabolism. BioMed Res. Int., 2018, 2018, 1-8.
[http://dx.doi.org/10.1155/2018/3087475] [PMID: 30498753]
[16]
Viola, K.L.; Klein, W.L. Amyloid β oligomers in Alzheimer’s disease pathogenesis, treatment, and diagnosis. Acta Neuropathol., 2015, 129(2), 183-206.
[http://dx.doi.org/10.1007/s00401-015-1386-3] [PMID: 25604547]
[17]
MacLeod, R.; Hillert, E.K.; Cameron, R.T.; Baillie, G.S. The role and therapeutic targeting of α-, β- and γ-secretase in Alzheimer’s disease. Future Sci. OA,, 2015, 1(3) fso.15.9.
[http://dx.doi.org/10.4155/fso.15.9] [PMID: 28031886]
[18]
Funamoto, S.; Tagami, S.; Okochi, M.; Morishima-Kawashima, M. Successive cleavage of β-amyloid precursor protein by γ-secretase. Semin. Cell Dev. Biol., 2020, 105, 64-74.
[http://dx.doi.org/10.1016/j.semcdb.2020.04.002] [PMID: 32354467]
[19]
Abdalla, A. Tau protein as a target for Alzheimer’s disease management. Saudi Pharm. J., 2015, 23(4), 405-406.
[http://dx.doi.org/10.1016/j.jsps.2015.01.017] [PMID: 27134542]
[20]
Medeiros, R.; Baglietto-Vargas, D.; LaFerla, F.M. The role of tau in Alzheimer’s disease and related disorders. CNS Neurosci. Ther., 2011, 17(5), 514-524.
[http://dx.doi.org/10.1111/j.1755-5949.2010.00177.x] [PMID: 20553310]
[21]
Ubersax, J.A.; Ferrell, J.E., Jr Mechanisms of specificity in protein phosphorylation. Nat. Rev. Mol. Cell Biol., 2007, 8(7), 530-541.
[http://dx.doi.org/10.1038/nrm2203] [PMID: 17585314]
[22]
Lee, V.M.Y.; Brunden, K.R.; Hutton, M.; Trojanowski, J.Q. Developing therapeutic approaches to tau, selected kinases, and related neuronal protein targets. Cold Spring Harb. Perspect. Med., 2011, 1(1), a006437.
[http://dx.doi.org/10.1101/cshperspect.a006437] [PMID: 22229117]
[23]
Steiner, B.; Mandelkow, E.M.; Biernat, J.; Gustke, N.; Meyer, H.E.; Schmidt, B.; Mieskes, G.; Söling, H.D.; Drechsel, D.; Kirschner, M.W.; Goedert, M.; Mandelkow, E. Phosphorylation of microtubule-associated protein tau: Identification of the site for Ca2(+)-calmodulin dependent kinase and relationship with tau phosphorylation in Alzheimer tangles. EMBO J., 1990, 9(11), 3539-3544.
[http://dx.doi.org/10.1002/j.1460-2075.1990.tb07563.x] [PMID: 2120043]
[24]
Braida, D.; Ponzoni, L.; Martucci, R.; Sparatore, F.; Gotti, C.; Sala, M. Role of neuronal Nicotinic Acetylcholine Receptors (nAChRs) on learning and memory in zebrafish. Psychopharmacology, 2014, 231(9), 1975-1985.
[http://dx.doi.org/10.1007/s00213-013-3340-1] [PMID: 24311357]
[25]
Hasselmo, M.E. The role of acetylcholine in learning and memory. Curr. Opin. Neurobiol., 2006, 16(6), 710-715.
[http://dx.doi.org/10.1016/j.conb.2006.09.002] [PMID: 17011181]
[26]
Ashford, J.W. Treatment of Alzheimer’s Disease: The legacy of the cholinergic hypothesis, neuroplasticity, and future directions. J. Alzheimers Dis., 2015, 47(1), 149-156.
[http://dx.doi.org/10.3233/JAD-150381] [PMID: 26402763]
[27]
Babic, T.; Francis, P.T.; Palmer, A.M.; Snape, M.; Wilcock, G.K. The cholinergic hypothesis of Alzheimer’s disease: A review of progress. J. Neurol. Neurosurg. Psychiatry, 1999, 67(4), 558-558.
[http://dx.doi.org/10.1136/jnnp.67.4.558] [PMID: 10610396]
[28]
Desai, A.K.; Grossberg, G.T. Diagnosis and treatment of Alzheimer’s disease. Neurology, 2005, 64, S34-S39.
[http://dx.doi.org/10.1212/WNL.64.12_suppl_3.S34] [PMID: 15994222]
[29]
Quirion, R. Cholinergic markers in Alzheimer disease and the autoregulation of acetylcholine release J. Psychiatry Neurosci., 1993, 18(5), 226-234.
[PMID: 8297921]
[30]
Ferreira-Vieira, T.H.; Guimaraes, I.M.; Silva, F.R.; Ribeiro, F.M. Alzheimer’s disease: Targeting the cholinergic system. Curr. Neuropharmacol., 2016, 14(1), 101-115.
[http://dx.doi.org/10.2174/1570159X13666150716165726] [PMID: 26813123]
[31]
Greig, N.H.; Utsuki, T.; Yu, Q.S.; Zhu, X.; Holloway, H.W.; Perry, T.; Lee, B.; Ingram, D.K.; Lahiri, D.K. A new therapeutic target in Alzheimer’s disease treatment: Attention to butyrylcholinesterase. Curr. Med. Res. Opin., 2001, 17(3), 159-165.
[http://dx.doi.org/10.1185/03007990152673800] [PMID: 11900310]
[32]
Mesulam, M.; Guillozet, A.; Shaw, P.; Quinn, B. Widely spread butyrylcholinesterase can hydrolyze acetylcholine in the normal and Alzheimer brain. Neurobiol. Dis., 2002, 9(1), 88-93.
[http://dx.doi.org/10.1006/nbdi.2001.0462] [PMID: 11848688]
[33]
Mesulam, M.M.; Guillozet, A.; Shaw, P.; Levey, A.; Duysen, E.G.; Lockridge, O. Acetylcholinesterase knockouts establish central cholinergic pathways and can use butyrylcholinesterase to hydrolyze acetylcholine. Neuroscience, 2002, 110(4), 627-639.
[http://dx.doi.org/10.1016/S0306-4522(01)00613-3] [PMID: 11934471]
[34]
Riedel, G.; Platt, B.; Micheau, J. Glutamate receptor function in learning and memory. Behav. Brain Res., 2003, 140(1-2), 1-47.
[http://dx.doi.org/10.1016/S0166-4328(02)00272-3] [PMID: 12644276]
[35]
Agatonovic-Kustrin, S.; Kettle, C.; Morton, D.W. A molecular approach in drug development for Alzheimer’s disease. Biomed. Pharmacother., 2018, 106, 553-565.
[http://dx.doi.org/10.1016/j.biopha.2018.06.147] [PMID: 29990843]
[36]
Danysz, W.; Parsons, C.G. The NMDA receptor antagonist memantine as a symptomatological and neuroprotective treatment for Alzheimer’s disease: Preclinical evidence. Int. J. Geriatr. Psychiatry, 2003, 18(S1), S23-S32.
[http://dx.doi.org/10.1002/gps.938] [PMID: 12973747]
[37]
Lleó, A. Current therapeutic options for Alzheimer’s disease. Curr. Genomics, 2007, 8(8), 550-558.
[http://dx.doi.org/10.2174/138920207783769549] [PMID: 19415128]
[38]
Esang, M.; Gupta, M. Aducanumab as a novel treatment for alzheimer’s disease: A decade of hope, controversies, and the future. Cureus, 2021, 13(8), e17591.
[http://dx.doi.org/10.7759/cureus.17591] [PMID: 34646644]
[39]
Beshir, S.A.; Aadithsoorya, A.M.; Parveen, A.; Goh, S.S.L.; Hussain, N.; Menon, V.B. Aducanumab therapy to treat Alzheimer’s disease: A narrative review. Int. J. Alzheimers Dis., 2022, 2022, 1-10.
[http://dx.doi.org/10.1155/2022/9343514] [PMID: 35308835]
[40]
Siddiqi, W.; Raza, G. Aducanumab- a drug of hope for the elderly. J. Pak. Med. Assoc., 2022, 72(2), 397.
[http://dx.doi.org/10.47391/JPMA.4418] [PMID: 35320210]
[41]
Wagstaff, A.J.; McTavish, D. Tacrine. Drugs Aging, 1994, 4(6), 510-540.
[http://dx.doi.org/10.2165/00002512-199404060-00006] [PMID: 7521234]
[42]
Gracon, S.I.; Knapp, M.J.; Berghoff, W.G.; Pierce, M.; DeJong, R.; Lobbestael, S.J.; Symons, J.; Dombey, S.L.; Luscombe, F.A.; Kraemer, D. Safety of tacrine: Clinical trials, treatment IND, and postmarketing experience. Alzheimer Dis. Assoc. Disord., 1998, 12(2), 93-101.
[http://dx.doi.org/10.1097/00002093-199806000-00007] [PMID: 9651138]
[43]
Madden, S.; Spaldin, V.; Park, B.K. Clinical pharmacokinetics of tacrine. Clin. Pharmacokinet., 1995, 28(6), 449-457.
[http://dx.doi.org/10.2165/00003088-199528060-00003] [PMID: 7656503]
[44]
Patocka, J.; Jun, D.; Kuca, K. Possible role of hydroxylated metabolites of tacrine in drug toxicity and therapy of Alzheimer’s disease. Curr. Drug Metab., 2008, 9(4), 332-335.
[http://dx.doi.org/10.2174/138920008784220619] [PMID: 18473751]
[45]
Schneider, S. L. A critical review of cholinesterase inhibitors as a treatment modality in Alzheimer’s disease. Dialogues Clin. Neurosci., 2000, 2(2), 111-128.
[http://dx.doi.org/10.31887/DCNS.2000.2.2/lschneider] [PMID: 22033801]
[46]
Cacabelos, R. Donepezil in Alzheimer’s disease: From conventional trials to pharmacogenetics Neuropsychiatr. Dis. Treat., 2007, 3(3), 303-333.
[PMID: 19300564]
[47]
Dooley, M.; Lamb, H.M. Donepezil. Drugs Aging, 2000, 16(3), 199-226.
[http://dx.doi.org/10.2165/00002512-200016030-00005] [PMID: 10803860]
[48]
Dong, H.; Yuede, C.M.; Coughlan, C.A.; Murphy, K.M.; Csernansky, J.G. Effects of donepezil on amyloid-β and synapse density in the Tg2576 mouse model of Alzheimer’s disease. Brain Res., 2009, 1303, 169-178.
[http://dx.doi.org/10.1016/j.brainres.2009.09.097] [PMID: 19799879]
[49]
Jann, M.W. Rivastigmine, a new-generation cholinesterase inhibitor for the treatment of Alzheimer’s disease. Pharmacotherapy, 2000, 20(1), 1-12.
[http://dx.doi.org/10.1592/phco.20.1.1.34664] [PMID: 10641971]
[50]
Farlow, M.R. Clinical pharmacokinetics of galantamine. Clin. Pharmacokinet., 2003, 42(15), 1383-1392.
[http://dx.doi.org/10.2165/00003088-200342150-00005] [PMID: 14674789]
[51]
Albertini, C.; Salerno, A.; Sena Murteira Pinheiro, P.; Bolognesi, M.L. From combinations to multitarget‐directed ligands: A continuum in Alzheimer’s disease polypharmacology. Med. Res. Rev., 2021, 41(5), 2606-2633.
[http://dx.doi.org/10.1002/med.21699] [PMID: 32557696]
[52]
Kumar, N.; Kumar, V.; Anand, P.; Kumar, V.; Ranjan Dwivedi, A.; Kumar, V. Advancements in the development of multi-target directed ligands for the treatment of Alzheimer’s disease. Bioorg. Med. Chem., 2022, 61, 116742.
[http://dx.doi.org/10.1016/j.bmc.2022.116742] [PMID: 35398739]
[53]
Maramai, S.; Benchekroun, M.; Gabr, M.T.; Yahiaoui, S. Multitarget therapeutic strategies for Alzheimer’s disease: Review on emerging target combinations. Biomed Res. Int., 2020, 2020, 5120230.
[http://dx.doi.org/10.1155/2020/5120230]
[54]
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]
[55]
Rochais, C.; Lecoutey, C.; Gaven, F.; Giannoni, P.; Hamidouche, K.; Hedou, D.; Dubost, E.; Genest, D.; Yahiaoui, S.; Freret, T.; Bouet, V.; Dauphin, F.; Sopkova de Oliveira Santos, J.; Ballandonne, C.; Corvaisier, S.; Malzert-Fréon, A.; Legay, R.; Boulouard, M.; Claeysen, S.; Dallemagne, P. Novel multitarget-directed ligands (MTDLs) with Acetylcholinesterase (AChE) inhibitory and serotonergic subtype 4 receptor (5-HT4R) agonist activities as potential agents against Alzheimer’s disease: The design of donecopride. J. Med. Chem., 2015, 58(7), 3172-3187.
[http://dx.doi.org/10.1021/acs.jmedchem.5b00115] [PMID: 25793650]
[56]
Rosini, M.; Andrisano, V.; Bartolini, M.; Bolognesi, M.L.; Hrelia, P.; Minarini, A.; Tarozzi, A.; Melchiorre, C. Rational approach to discover multipotent anti-Alzheimer drugs. J. Med. Chem., 2005, 48(2), 360-363.
[http://dx.doi.org/10.1021/jm049112h] [PMID: 15658850]
[57]
Marco-Contelles, J.; León, R.; de los Ríos, C.; Guglietta, A.; Terencio, J.; López, M.G.; García, A.G.; Villarroya, M. Novel multipotent tacrine-dihydropyridine hybrids with improved acetylcholinesterase inhibitory and neuroprotective activities as potential drugs for the treatment of Alzheimer’s disease. J. Med. Chem., 2006, 49(26), 7607-7610.
[http://dx.doi.org/10.1021/jm061047j] [PMID: 17181144]
[58]
Fernández-Bachiller, M.I.; Pérez, C.; Monjas, L.; Rademann, J.; Rodríguez-Franco, M.I. New tacrine-4-oxo-4H-chromene hybrids as multifunctional agents for the treatment of Alzheimer’s disease, with cholinergic, antioxidant, and β-amyloid-reducing properties. J. Med. Chem., 2012, 55(3), 1303-1317.
[http://dx.doi.org/10.1021/jm201460y] [PMID: 22243648]
[59]
Cai, Z. Monoamine oxidase inhibitors: Promising therapeutic agents for Alzheimer’s disease. Mol. Med. Rep., 2014, 9(5), 1533-1541.
[http://dx.doi.org/10.3892/mmr.2014.2040] [PMID: 24626484]
[60]
Lu, C.; Zhou, Q.; Yan, J.; Du, Z.; Huang, L.; Li, X. A novel series of tacrine–selegiline hybrids with cholinesterase and monoamine oxidase inhibition activities for the treatment of Alzheimer’s disease. Eur. J. Med. Chem., 2013, 62, 745-753.
[http://dx.doi.org/10.1016/j.ejmech.2013.01.039] [PMID: 23454517]
[61]
Xie, S.S.; Wang, X.; Jiang, N.; Yu, W.; Wang, K.D.G.; Lan, J.S.; Li, Z.R.; Kong, L.Y. Multi-target tacrine-coumarin hybrids: Cholinesterase and monoamine oxidase B inhibition properties against Alzheimer’s disease. Eur. J. Med. Chem., 2015, 95, 153-165.
[http://dx.doi.org/10.1016/j.ejmech.2015.03.040] [PMID: 25812965]
[62]
Xie, S.S.; Lan, J.S.; Wang, X.B.; Jiang, N.; Dong, G.; Li, Z.R.; Wang, K.D.G.; Guo, P.P.; Kong, L.Y. Multifunctional tacrine–trolox hybrids for the treatment of Alzheimer’s disease with cholinergic, antioxidant, neuroprotective and hepatoprotective properties. Eur. J. Med. Chem., 2015, 93, 42-50.
[http://dx.doi.org/10.1016/j.ejmech.2015.01.058] [PMID: 25656088]
[63]
Zhang, C.; Du, Q.Y.; Chen, L.D.; Wu, W.H.; Liao, S.Y.; Yu, L.H.; Liang, X.T. Design, synthesis and evaluation of novel tacrine-multialkoxybenzene hybrids as multi-targeted compounds against Alzheimer’s disease. Eur. J. Med. Chem., 2016, 116, 200-209.
[http://dx.doi.org/10.1016/j.ejmech.2016.03.077] [PMID: 27061983]
[64]
Pourabdi, L.; Khoobi, M.; Nadri, H.; Moradi, A.; Moghadam, F.H.; Emami, S.; Mojtahedi, M.M.; Haririan, I.; Forootanfar, H.; Ameri, A.; Foroumadi, A.; Shafiee, A. Synthesis and structure-activity relationship study of tacrine-based pyrano[2,3-c]pyrazoles targeting AChE/BuChE and 15-LOX. Eur. J. Med. Chem., 2016, 123, 298-308.
[http://dx.doi.org/10.1016/j.ejmech.2016.07.043] [PMID: 27484515]
[65]
Najafi, Z.; Mahdavi, M.; Saeedi, M.; Karimpour-Razkenari, E.; Asatouri, R.; Vafadarnejad, F.; Moghadam, F.H.; Khanavi, M.; Sharifzadeh, M.; Akbarzadeh, T. Novel tacrine-1,2,3-triazole hybrids: In vitro, in vivo biological evaluation and docking study of cholinesterase inhibitors. Eur. J. Med. Chem., 2017, 125, 1200-1212.
[http://dx.doi.org/10.1016/j.ejmech.2016.11.008] [PMID: 27863370]
[66]
Eghtedari, M.; Sarrafi, Y.; Nadri, H.; Mahdavi, M.; Moradi, A.; Homayouni Moghadam, F.; Emami, S.; Firoozpour, L.; Asadipour, A.; Sabzevari, O.; Foroumadi, A. New tacrine-derived AChE/BuChE inhibitors: Synthesis and biological evaluation of 5-amino-2-phenyl-4H-pyrano[2,3-b]quinoline-3-carboxylates. Eur. J. Med. Chem., 2017, 128, 237-246.
[http://dx.doi.org/10.1016/j.ejmech.2017.01.042] [PMID: 28189905]
[67]
Jalili-Baleh, L.; Nadri, H.; Moradi, A.; Bukhari, S.N.A.; Shakibaie, M.; Jafari, M.; Golshani, M.; Homayouni Moghadam, F.; Firoozpour, L.; Asadipour, A.; Emami, S.; Khoobi, M.; Foroumadi, A. New racemic annulated pyrazolo[1,2-b]phthalazines as tacrine-like AChE inhibitors with potential use in Alzheimer’s disease. Eur. J. Med. Chem., 2017, 139, 280-289.
[http://dx.doi.org/10.1016/j.ejmech.2017.07.072] [PMID: 28803044]
[68]
Reddy, E.K.; Remya, C.; Mantosh, K.; Sajith, A.M.; Omkumar, R.V.; Sadasivan, C.; Anwar, S. Novel tacrine derivatives exhibiting improved acetylcholinesterase inhibition: Design, synthesis and biological evaluation. Eur. J. Med. Chem., 2017, 139, 367-377.
[http://dx.doi.org/10.1016/j.ejmech.2017.08.013] [PMID: 28810188]
[69]
Li, G.; Hong, G.; Li, X.; Zhang, Y.; Xu, Z.; Mao, L.; Feng, X.; Liu, T. Synthesis and activity towards Alzheimer’s disease in vitro: Tacrine, phenolic acid and ligustrazine hybrids. Eur. J. Med. Chem., 2018, 148, 238-254.
[http://dx.doi.org/10.1016/j.ejmech.2018.01.028] [PMID: 29466774]
[70]
Roldán-Peña, J.M.; Romero-Real, V.; Hicke, J.; Maya, I.; Franconetti, A.; Lagunes, I.; Padrón, J.M.; Petralla, S.; Poeta, E.; Naldi, M.; Bartolini, M.; Monti, B.; Bolognesi, M.L.; López, Ó.; Fernández-Bolaños, J.G. Tacrine-O-protected phenolics heterodimers as multitarget-directed ligands against Alzheimer’s disease: Selective subnanomolar BuChE inhibitors. Eur. J. Med. Chem., 2019, 181, 111550.
[http://dx.doi.org/10.1016/j.ejmech.2019.07.053] [PMID: 31376562]
[71]
Derabli, C.; Boulebd, H.; Abdelwahab, A.B.; Boucheraine, C.; Zerrouki, S.; Bensouici, C.; Kirsch, G.; Boulcina, R.; Debache, A. Synthesis, biological evaluation and molecular docking studies of novel 2-alkylthiopyrimidino-tacrines as anticholinesterase agents and their DFT calculations. J. Mol. Struct., 2020, 1209, 127902.
[http://dx.doi.org/10.1016/j.molstruc.2020.127902]
[72]
Remya, C.; Dileep, K.V.; Koti Reddy, E.; Mantosh, K.; Lakshmi, K.; Sarah Jacob, R.; Sajith, A.M.; Jayadevi Variyar, E.; Anwar, S.; Zhang, K.Y.J.; Sadasivan, C.; Omkumar, R.V. Neuroprotective derivatives of tacrine that target NMDA receptor and acetyl cholinesterase – Design, synthesis and biological evaluation. Comput. Struct. Biotechnol. J., 2021, 19, 4517-4537.
[http://dx.doi.org/10.1016/j.csbj.2021.07.041] [PMID: 34471497]
[73]
Ip, F.C.F.; Fu, G.; Yang, F.; Kang, F.; Sun, P.; Ling, C.Y.; Cheung, K.; Xie, F.; Hu, Y.; Fu, L. A tacrine-tetrahydroquinoline heterodimer potently inhibits acetylcholinesterase activity and enhances neurotransmission in mice. Eur. J. Med. Chem., 2021, 226, 113827.
[http://dx.doi.org/10.1016/j.ejmech.2021.113827] [PMID: 34530383]
[74]
Zhang, P.; Wang, Z.; Mou, C.; Zou, J.; Xie, Y.; Liu, Z.; Benjamin Naman, C.; Mao, Y.; Wei, J.; Huang, X.; Dong, J.; Yang, M.; Wang, N.; Jin, H.; Liu, F.; Lin, D.; Liu, H.; Zhou, F.; He, S.; Zhang, B.; Cui, W. Design and synthesis of novel tacrine dipicolylamine dimers that are multiple-target-directed ligands with potential to treat Alzheimer’s disease. Bioorg. Chem., 2021, 116, 105387.
[http://dx.doi.org/10.1016/j.bioorg.2021.105387] [PMID: 34628225]
[75]
Kaur Gulati, H.; Choudhary, S.; Kumar, N.; Ahmed, A.; Bhagat, K.; Vir Singh, J.; Singh, A.; Kumar, A.; Singh Bedi, P.M.; Singh, H.; Mukherjee, D. Design, Synthesis, biological investigations and molecular interactions of triazole linked tacrine glycoconjugates as Acetylcholinesterase inhibitors with reduced hepatotoxicity. Bioorg. Chem., 2022, 118, 105479.
[http://dx.doi.org/10.1016/j.bioorg.2021.105479] [PMID: 34801945]
[76]
Sadafi Kohnehshahri, M.; Chehardoli, G.; Bahiraei, M.; Akbarzadeh, T.; Ranjbar, A.; Rastegari, A.; Najafi, Z. Novel tacrine-based acetylcholinesterase inhibitors as potential agents for the treatment of Alzheimer’s disease: Quinolotacrine hybrids. Mol. Divers., 2022, 26(1), 489-503.
[http://dx.doi.org/10.1007/s11030-021-10307-2] [PMID: 34491490]
[77]
Grishchenko, M.V.; Makhaeva, G.F.; Burgart, Y.V.; Rudakova, E.V.; Boltneva, N.P.; Kovaleva, N.V.; Serebryakova, O.G.; Lushchekina, S.V.; Astakhova, T.Y.; Zhilina, E.F.; Shchegolkov, E.V.; Richardson, R.J.; Saloutin, V.I. Conjugates of tacrine with salicylamide as promising multitarget agents for Alzheimer’s disease. ChemMedChem, 2022, 17(10), e202200080.
[http://dx.doi.org/10.1002/cmdc.202200080] [PMID: 35322571]
[78]
Rastegari, A.; Safavi, M.; Vafadarnejad, F.; Najafi, Z.; Hariri, R.; Bukhari, S.N.A.; Iraji, A.; Edraki, N.; Firuzi, O.; Saeedi, M.; Mahdavi, M.; Akbarzadeh, T. Synthesis and evaluation of novel arylisoxazoles linked to tacrine moiety: In vitro and in vivo biological activities against Alzheimer’s disease. Mol. Divers., 2022, 26(1), 409-428.
[http://dx.doi.org/10.1007/s11030-021-10248-w] [PMID: 34273065]
[79]
Przybyłowska, M.; Dzierzbicka, K.; Kowalski, S.; Demkowicz, S.; Daśko, M.; Inkielewicz-Stepniak, I. Design, synthesis and biological evaluation of novel N -phosphorylated and O -phosphorylated tacrine derivatives as potential drugs against Alzheimer’s disease. J. Enzyme Inhib. Med. Chem., 2022, 37(1), 1012-1022.
[http://dx.doi.org/10.1080/14756366.2022.2045591] [PMID: 35361039]
[80]
Hui, A.; Chen, Y.; Zhu, S.; Gan, C.; Pan, J.; Zhou, A. Design and synthesis of tacrine-phenothiazine hybrids as multitarget drugs for Alzheimer’s disease. Med. Chem. Res., 2014, 23(7), 3546-3557.
[http://dx.doi.org/10.1007/s00044-014-0931-2]
[81]
Mahmoud, Z.; Mohamed, L.W.; Mohamed, K.O.; Sayed, H.S. Recent modifications of anti-dementia agents focusing on tacrine and/or donepezil analogs. Med. Chem., 2022, 18.
[http://dx.doi.org/10.2174/1573406418666220827155615] [PMID: 36043761]
[82]
Tian, S.; Huang, Z.; Meng, Q.; Liu, Z. Multi-target drug design of anti-Alzheimer’s disease based on tacrine. Mini Rev. Med. Chem., 2021, 21(15), 2039-2064.
[http://dx.doi.org/10.2174/1389557521666210212151127] [PMID: 33583371]
[83]
Ramalakshmi, N. Multitarget directed ligand approaches for Alzheimer’s disease: A comprehensive review. Mini Rev. Med. Chem., 2021, 21(16), 2361-2388.
[http://dx.doi.org/10.2174/1389557521666210405161205] [PMID: 33820504]

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