A Systematic Review on Donepezil-based Derivatives as Potential Cholinesterase Inhibitors for Alzheimer’s Disease

Author(s): Jan Korabecny, Katarina Spilovska, Eva Mezeiova, Ondrej Benek, Radomir Juza, Daniel Kaping, Ondrej Soukup*.

Journal Name: Current Medicinal Chemistry

Volume 26 , Issue 30 , 2019

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Alzheimer’s Disease (AD) is a multifactorial progressive neurodegenerative disorder characterized by memory loss, disorientation, and gradual deterioration of intellectual capacity. Its etiology has not been elucidated yet. To date, only one therapeutic approach has been approved for the treatment of AD. The pharmacotherapy of AD has relied on noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist - memantine, and acetylcholinesterase (AChE) inhibitors (AChEIs) - tacrine, donepezil, rivastigmine and galantamine. Donepezil was able to ameliorate the symptoms related to AD mainly via AChE, but also through reduction of β-amyloid burden. This review presents the overview of donepezilrelated compounds as potential anti-AD drugs developed on the basis of cholinergic hypothesis to act as solely AChE and butyrylcholinesterase (BChE) inhibitors.

Keywords: Alzheimer’s disease, acetylcholinesterase, butyrylcholinesterase, donepezil, inhibitor, treatment, NMDA.

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]
Maresova, P.; Klimova, B.; Novotny, M.; Kuca, K. Alzheimer’s and parkinson’s diseases: expected economic impact on europe-a call for a uniform european strategy. J. Alzheimers Dis., 2016, 54(3), 1123-1133.
[http://dx.doi.org/10.3233/JAD-160484] [PMID: 27567862]
Alzheimer’s Association 2015 Alzheimer’s disease facts and figures. Alzheimers Dement., 2015, 11(3), 332-384.
[http://dx.doi.org/10.1016/j.jalz.2015.02.003] [PMID: 25984581]
Reitz, C.; Brayne, C.; Mayeux, R. Epidemiology of Alzheimer disease. Nat. Rev. Neurol., 2011, 7(3), 137-152.
[http://dx.doi.org/10.1038/nrneurol.2011.2] [PMID: 21304480]
Kuca, K.; Soukup, O.; Maresova, P.; Korabecny, J.; Nepovimova, E.; Klimova, B.; Honegr, J.; Ramalho, T.C.; França, T.C.C. Current approaches against alzheimer’s disease in clinical trials. J. Braz. Chem. Soc., 2016, 27, 641-649.
Kalaria, R.N.; Maestre, G.E.; Arizaga, R.; Friedland, R.P.; Galasko, D.; Hall, K.; Luchsinger, J.A.; Ogunniyi, A.; Perry, E.K.; Potocnik, F.; Prince, M.; Stewart, R.; Wimo, A.; Zhang, Z-X.; Antuono, P. World federation of neurology dementia research group. alzheimer’s disease and vascular dementia in developing countries: prevalence, management, and risk factors. Lancet Neurol., 2008, 7(9), 812-826.
[http://dx.doi.org/10.1016/S1474-4422(08)70169-8] [PMID: 18667359]
Walker, L.C.; Diamond, M.I.; Duff, K.E.; Hyman, B.T. Mechanisms of protein seeding in neurodegenerative diseases. JAMA Neurol., 2013, 70(3), 304-310.
[http://dx.doi.org/10.1001/jamaneurol.2013.1453] [PMID: 23599928]
Davies, P.; Maloney, A.J. Selective loss of central cholinergic neurons in Alzheimer’s disease. Lancet, 1976, 2(8000), 1403.
[http://dx.doi.org/10.1016/S0140-6736(76)91936-X] [PMID: 63862]
Drachman, D.A.; Leavitt, J. Human memory and the cholinergic system. A relationship to aging? Arch. Neurol., 1974, 30(2), 113-121.
[http://dx.doi.org/10.1001/archneur.1974.00490320001001] [PMID: 4359364]
Longo, V.G. Behavioral and electroencephalographic effects of atropine and related compounds. Pharmacol. Rev., 1966, 18(2), 965-996.
[PMID: 5328390]
Klimova, B.; Kuca, K. Alzheimer’s disease: potential preventive, non-invasive, intervention strategies in lowering the risk of cognitive decline - a review study. J. Appl. Biomed., 2015, 13, 257-261.
Klimova, B.; Maresova, P.; Kuca, K. Non-pharmacological approaches to the prevention and treatment of alzheimer’s disease with respect to the rising treatment costs. Curr. Alzheimer Res., 2016, 13(11), 1249-1258.
[http://dx.doi.org/10.2174/1567205013666151116142302] [PMID: 26567732]
Greig, N.H.; Utsuki, T.; Yu, Q.; 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]
Guillozet, A.L.; Smiley, J.F.; Mash, D.C.; Mesulam, M.M. Butyrylcholinesterase in the life cycle of amyloid plaques. Ann. Neurol., 1997, 42(6), 909-918.
[http://dx.doi.org/10.1002/ana.410420613] [PMID: 9403484]
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-beta-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]
Lehmann, D.J.; Johnston, C.; Smith, A.D. Synergy between the genes for butyrylcholinesterase K variant and apolipoprotein E4 in late-onset confirmed Alzheimer’s disease. Hum. Mol. Genet., 1997, 6(11), 1933-1936.
[http://dx.doi.org/10.1093/hmg/6.11.1933] [PMID: 9302273]
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]
Doody, R.S.; Thomas, R.G.; Farlow, M.; Iwatsubo, T.; Vellas, B.; Joffe, S.; Kieburtz, K.; Raman, R.; Sun, X.; Aisen, P.S.; Siemers, E.; Liu-Seifert, H.; Mohs, R. Phase 3 trials of solanezumab for mild-to-moderate Alzheimer’s disease. N. Engl. J. Med., 2014, 370(4), 311-321.
[http://dx.doi.org/10.1056/NEJMoa1312889] [PMID: 24450890]
Korábecný, J.; Hrubá, E.; Soukup, O.; Zemek, F.; Musílek, K.; Nepovímová, E.; Spilovská, K.; Opletalová, V.; Kuca, K. [Intended pharmacotherapeutical approaches of Alzheimer’s disease therapy Ceska Slov. Farm., 2012, 61(1-2), 4-10.
[PMID: 22536646]
Salloway, S.; Sperling, R.; Fox, N.C.; Blennow, K.; Klunk, W.; Raskind, M.; Sabbagh, M.; Honig, L.S.; Porsteinsson, A.P.; Ferris, S.; Reichert, M.; Ketter, N.; Nejadnik, B.; Guenzler, V.; Miloslavsky, M.; Wang, D.; Lu, Y.; Lull, J.; Tudor, I.C.; Liu, E.; Grundman, M.; Yuen, E.; Black, R.; Brashear, H.R. Bapineuzumab 301 and 302 Clinical Trial Investigators Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s disease. N. Engl. J. Med., 2014, 370(4), 322-333.
[http://dx.doi.org/10.1056/NEJMoa1304839] [PMID: 24450891]
Korábečný, J.; Spilovská, K.; Benek, O.; Musílek, K.; Soukup, O.; Kuča, K. [Tacrine and its derivatives in the therapy of Alzheimers disease] Ceska Slov. Farm., 2012, 61(5), 210-221.
[PMID: 23256654]
Soukup, O.; Jun, D.; Zdarova-Karasova, J.; Patocka, J.; Musilek, K.; Korabecny, J.; Krusek, J.; Kaniakova, M.; Sepsova, V.; Mandikova, J.; Trejtnar, F.; Pohanka, M.; Drtinova, L.; Pavlik, M.; Tobin, G.; Kuca, K. A resurrection of 7-MEOTA: a comparison with tacrine. Curr. Alzheimer Res., 2013, 10(8), 893-906.
[http://dx.doi.org/10.2174/1567205011310080011] [PMID: 24093535]
Watkins, P.B.; Zimmerman, H.J.; Knapp, M.J.; Gracon, S.I.; Lewis, K.W. Hepatotoxic effects of tacrine administration in patients with Alzheimer’s disease. JAMA, 1994, 271(13), 992-998.
[http://dx.doi.org/10.1001/jama.1994.03510370044030] [PMID: 8139084]
Winker, M.A. Tacrine for Alzheimer’s disease. Which patient, what dose? JAMA, 1994, 271(13), 1023-1024.
[http://dx.doi.org/10.1001/jama.1994.03510370075036] [PMID: 8139061]
Spilovska, K.; Korabecny, J.; Nepovimova, E.; Dolezal, R.; Mezeiova, E.; Soukup, O.; Kuca, K. multitarget tacrine hybrids with neuroprotective properties to confront alzheimer’s disease. Curr. Top. Med. Chem., 2017, 17(9), 1006-1026.
[http://dx.doi.org/10.2174/1568026605666160927152728] [PMID: 27697055]
Korabecny, J.; Zemek, F.; Soukup, O.; Spilovská, K.; Musilek, K.; Jun, D.; Nepovímová, E.; Kuca, K. Pharmacotherapy of alzheimer’s disease: current state and future perspectives. Frontiers in Drug Design and Discovery, 2014, 2014, 3-39.
Zemek, F.; Drtinova, L.; Nepovimova, E.; Sepsova, V.; Korabecny, J.; Klimes, J.; Kuca, K. Outcomes of Alzheimer’s disease therapy with acetylcholinesterase inhibitors and memantine. Expert Opin. Drug Saf., 2014, 13(6), 759-774.
[http://dx.doi.org/ 10.1517/14740338.2014.914168] [PMID: 24845946]
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]
Parsons, C.G.; Danysz, W.; Dekundy, A.; Pulte, I. Memantine and cholinesterase inhibitors: complementary mechanisms in the treatment of Alzheimer’s disease. Neurotox. Res., 2013, 24(3), 358-369.
[http://dx.doi.org/10.1007/s12640-013-9398-z] [PMID: 23657927]
Sonkusare, S.K.; Kaul, C.L.; Ramarao, P. Dementia of Alzheimer’s disease and other neurodegenerative disorders--memantine, a new hope. Pharmacol. Res., 2005, 51(1), 1-17.
[http://dx.doi.org/10.1016/j.phrs.2004.05.005] [PMID: 15519530]
Spilovska, K.; Zemek, F.; Korabecny, J.; Nepovimova, E.; Soukup, O.; Windisch, M.; Kuca, K. Adamantane - a lead structure for drugs in clinical practice. Curr. Med. Chem., 2016, 23(29), 3245-3266.
[http://dx.doi.org/10.2174/0929867323666160525114026] [PMID: 27222266]
Horak, M.; Holubova, K.; Nepovimova, E.; Krusek, J.; Kaniakova, M.; Korabecny, J.; Vyklicky, L.; Kuca, K.; Stuchlik, A.; Ricny, J.; Vales, K.; Soukup, O. The pharmacology of tacrine at N-methyl-d-aspartate receptors. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2017, 75, 54-62.
[http://dx.doi.org/10.1016/j.pnpbp.2017.01.003] [PMID: 28089695]
Knowles, J. Donepezil in Alzheimer’s disease: an evidence-based review of its impact on clinical and economic outcomes. Core Evid., 2006, 1(3), 195-219.
[PMID: 22500154]
Lee, J-H.; Jeong, S-K.; Kim, B.C.; Park, K.W.; Dash, A. Donepezil across the spectrum of Alzheimer’s disease: dose optimization and clinical relevance. Acta Neurol. Scand., 2015, 131(5), 259-267.
[http://dx.doi.org/10.1111/ane.12386] [PMID: 25690270]
Jelic, V.; Darreh-Shori, T. Donepezil: A review of pharmacological characteristics and role in the management of alzheimer disease. Clin. Med. Insights Ther., 2010, 771.
Cheewakriengkrai, L.; Gauthier, S. A 10-year perspective on donepezil. Expert Opin. Pharmacother., 2013, 14(3), 331-338.
[http://dx.doi.org/10.1517/14656566.2013.760543] [PMID: 23316713]
Cheung, J.; Rudolph, M.J.; Burshteyn, F.; Cassidy, M.S.; Gary, E.N.; Love, J.; Franklin, M.C.; Height, J.J. Structures of human acetylcholinesterase in complex with pharmacologically important ligands. J. Med. Chem., 2012, 55(22), 10282-10286.
[http://dx.doi.org/10.1021/jm300871x] [PMID: 23035744]
Kryger, G.; Silman, I.; Sussman, J.L. Structure of acetylcholinesterase complexed with E2020 (Aricept): implications for the design of new anti-Alzheimer drugs. Structure, 1999, 7(3), 297-307.
[http://dx.doi.org/10.1016/S0969-2126(99)80040-9] [PMID: 10368299]
Bolognesi, M.L.; Andrisano, V.; Bartolini, M.; Banzi, R.; Melchiorre, C. Propidium-based polyamine ligands as potent inhibitors of acetylcholinesterase and acetylcholinesterase-induced amyloid-beta aggregation. J. Med. Chem., 2005, 48(1), 24-27.
[http://dx.doi.org/10.1021/jm049156q] [PMID: 15633997]
Hamulakova, S.; Janovec, L.; Hrabinova, M.; Spilovska, K.; Korabecny, J.; Kristian, P.; Kuca, K.; Imrich, J. Synthesis and biological evaluation of novel tacrine derivatives and tacrine-coumarin hybrids as cholinesterase inhibitors. J. Med. Chem., 2014, 57(16), 7073-7084.
[http://dx.doi.org/10.1021/jm5008648] [PMID: 25089370]
Muñoz-Ruiz, P.; Rubio, L.; García-Palomero, E.; Dorronsoro, I.; del Monte-Millán, M.; Valenzuela, R.; Usán, P.; de Austria, C.; Bartolini, M.; Andrisano, V.; Bidon-Chanal, A.; Orozco, M.; Luque, F.J.; Medina, M.; Martínez, A. Design, synthesis, and biological evaluation of dual binding site acetylcholinesterase inhibitors: new disease-modifying agents for Alzheimer’s disease. J. Med. Chem., 2005, 48(23), 7223-7233.
[http://dx.doi.org/10.1021/jm0503289] [PMID: 16279781]
Nepovimova, E.; Uliassi, E.; Korabecny, J.; Peña-Altamira, L.E.; Samez, S.; Pesaresi, A.; Garcia, G.E.; Bartolini, M.; Andrisano, V.; Bergamini, C.; Fato, R.; Lamba, D.; Roberti, M.; Kuca, K.; Monti, B.; Bolognesi, M.L. Multitarget drug design strategy: quinone-tacrine hybrids designed to block amyloid-β aggregation and to exert anticholinesterase and antioxidant effects. J. Med. Chem., 2014, 57(20), 8576-8589.
[http://dx.doi.org/10.1021/jm5010804] [PMID: 25259726]
Panek, D.; Więckowska, A.; Wichur, T.; Bajda, M.; Godyń, J.; Jończyk, J.; Mika, K.; Janockova, J.; Soukup, O.; Knez, D.; Korabecny, J.; Gobec, S.; Malawska, B. Design, synthesis and biological evaluation of new phthalimide and saccharin derivatives with alicyclic amines targeting cholinesterases, beta-secretase and amyloid beta aggregation. Eur. J. Med. Chem., 2017, 125, 676-695.
[http://dx.doi.org/10.1016/j.ejmech.2016.09.078] [PMID: 27721153]
Spilovska, K.; Korabecny, J.; Sepsova, V.; Jun, D.; Hrabinova, M.; Jost, P.; Muckova, L.; Soukup, O.; Janockova, J.; Kucera, T.; Dolezal, R.; Mezeiova, E.; Kaping, D.; Kuca, K. Novel tacrine-scutellarin hybrids as multipotent anti-alzheimer’s agents: design, synthesis and biological evaluation. Molecules, 2017, 22(6) pii: E1006
[http://dx.doi.org/10.3390/molecules22061006] [PMID: 28621747]
De Ferrari, G.V.; Canales, M.A.; Shin, I.; Weiner, L.M.; Silman, I.; Inestrosa, N.C. A structural motif of acetylcholinesterase that promotes amyloid beta-peptide fibril formation. Biochemistry, 2001, 40(35), 10447-10457.
[http://dx.doi.org/10.1021/bi0101392] [PMID: 11523986]
Jacobson, S.A.; Sabbagh, M.N. Donepezil: potential neuroprotective and disease-modifying effects. Expert Opin. Drug Metab. Toxicol., 2008, 4(10), 1363-1369.
[http://dx.doi.org/10.1517/17425255.4.10.1363] [PMID: 18798705]
Beach, T.G.; Potter, P.E.; Kuo, Y.M.; Emmerling, M.R.; Durham, R.A.; Webster, S.D.; Walker, D.G.; Sue, L.I.; Scott, S.; Layne, K.J.; Roher, A.E. Cholinergic deafferentation of the rabbit cortex: a new animal model of Abeta deposition. Neurosci. Lett., 2000, 283(1), 9-12.
[http://dx.doi.org/10.1016/S0304-3940(00)00916-2] [PMID: 10729621]
Kume, T.; Sugimoto, M.; Takada, Y.; Yamaguchi, T.; Yonezawa, A.; Katsuki, H.; Sugimoto, H.; Akaike, A. Up-regulation of nicotinic acetylcholine receptors by central-type acetylcholinesterase inhibitors in rat cortical neurons. Eur. J. Pharmacol., 2005, 527(1-3), 77-85.
[http://dx.doi.org/10.1016/j.ejphar.2005.10.028] [PMID: 16313899]
Takada-Takatori, Y.; Kume, T.; Sugimoto, M.; Katsuki, H.; Sugimoto, H.; Akaike, A. Acetylcholinesterase inhibitors used in treatment of Alzheimer’s disease prevent glutamate neurotoxicity via nicotinic acetylcholine receptors and phosphatidylinositol 3-kinase cascade. Neuropharmacology, 2006, 51(3), 474-486.
[http://dx.doi.org/10.1016/j.neuropharm.2006.04.007] [PMID: 16762377]
Nordberg, A. Mechanisms behind the neuroprotective actions of cholinesterase inhibitors in Alzheimer disease. Alzheimer Dis. Assoc. Disord., 2006, 20(2)(Suppl. 1), S12-S18.
[http://dx.doi.org/10.1097/01.wad.0000213804.59187.2d] [PMID: 16772751]
Chen, X.; Magnotta, V.A.; Duff, K.; Boles Ponto, L.L.; Schultz, S.K. Donepezil effects on cerebral blood flow in older adults with mild cognitive deficits. J. Neuropsychiatry Clin. Neurosci., 2006, 18(2), 178-185.
[http://dx.doi.org/10.1176/jnp.2006.18.2.178] [PMID: 16720794]
Tsukada, H.; Sato, K.; Kakiuchi, T.; Nishiyama, S. Age-related impairment of coupling mechanism between neuronal activation and functional cerebral blood flow response was restored by cholinesterase inhibition: PET study with microdialysis in the awake monkey brain. Brain Res., 2000, 857(1-2), 158-164.
[http://dx.doi.org/10.1016/S0006-8993(99)02394-X] [PMID: 10700563]
Cummings, J.L.; Geldmacher, D.; Farlow, M.; Sabbagh, M.; Christensen, D.; Betz, P. High-dose donepezil (23 mg/day) for the treatment of moderate and severe Alzheimer’s disease: drug profile and clinical guidelines. CNS Neurosci. Ther., 2013, 19(5), 294-301.
[http://dx.doi.org/10.1111/cns.12076] [PMID: 23462265]
Darreh-Shori, T.; Meurling, L.; Pettersson, T.; Hugosson, K.; Hellström-Lindahl, E.; Andreasen, N.; Minthon, L.; Nordberg, A. Changes in the activity and protein levels of CSF acetylcholinesterases in relation to cognitive function of patients with mild Alzheimer’s disease following chronic donepezil treatment. J. Neural Transm. (Vienna), 2006, 113(11), 1791-1801.
[http://dx.doi.org/10.1007/s00702-006-0526-2] [PMID: 16868793]
Taylor, P.; Lappi, S. Interaction of fluorescence probes with acetylcholinesterase. The site and specificity of propidium binding. Biochemistry, 1975, 14(9), 1989-1997.
[http://dx.doi.org/10.1021/bi00680a029] [PMID: 1125207]
Inestrosa, N.C.; Dinamarca, M.C.; Alvarez, A. Amyloid-cholinesterase interactions. Implications for Alzheimer’s disease. FEBS J., 2008, 275(4), 625-632.
[http://dx.doi.org/10.1111/j.1742-4658.2007.06238.x] [PMID: 18205831]
Mohs, R.C.; Doody, R.S.; Morris, J.C.; Ieni, J.R.; Rogers, S.L.; Perdomo, C.A.; Pratt, R.D. “312” Study Group. A 1-year, placebo-controlled preservation of function survival study of donepezil in AD patients. Neurology, 2001, 57(3), 481-488.
[http://dx.doi.org/10.1212/WNL.57.3.481] [PMID: 11502917]
Sugimoto, H.; Tsuchiya, Y.; Sugumi, H.; Higurashi, K.; Karibe, N.; Iimura, Y.; Sasaki, A.; Kawakami, Y.; Nakamura, T.; Araki, S. Novel piperidine derivatives. Synthesis and anti-acetylcholinesterase activity of 1-benzyl-4-[2-(N-benzoylamino)ethyl]piperidine derivatives. J. Med. Chem., 1990, 33(7), 1880-1887.
[http://dx.doi.org/10.1021/jm00169a008] [PMID: 2362265]
Sugimoto, H.; Ogura, H.; Arai, Y.; Limura, Y.; Yamanishi, Y. Research and development of donepezil hydrochloride, a new type of acetylcholinesterase inhibitor. Jpn. J. Pharmacol., 2002, 89(1), 7-20.
[http://dx.doi.org/10.1254/jjp.89.7] [PMID: 12083745]
Sugimoto, H.; Iimura, Y.; Yamanishi, Y.; Yamatsu, K. Synthesis and structure-activity relationships of acetylcholinesterase inhibitors: 1-benzyl-4-[(5,6-dimethoxy-1-oxoindan-2-yl)methyl]piperidine hydrochloride and related compounds. J. Med. Chem., 1995, 38(24), 4821-4829.
[http://dx.doi.org/10.1021/jm00024a009] [PMID: 7490731]
Sugimoto, H.; Iimura, Y.; Yamanishi, Y.; Yamatsu, K. Synthesis and anti-acetylcholinesterase activity of 1-Benzyl-4-[(5,6-Dimethoxy-1-Indanon-2-Yl)Methyl]piperidine hydrochloride (E2020) and related compounds. Bioorg. Med. Chem. Lett., 1992, 2, 871-876.
Cardozo, M.G.; Iimura, Y.; Sugimoto, H.; Yamanishi, Y.; Hopfinger, A.J. QSAR analyses of the substituted indanone and benzylpiperidine rings of a series of indanone-benzylpiperidine inhibitors of acetylcholinesterase. J. Med. Chem., 1992, 35(3), 584-589.
[http://dx.doi.org/10.1021/jm00081a022] [PMID: 1738151]
Cardozo, M.G.; Kawai, T.; Iimura, Y.; Sugimoto, H.; Yamanishi, Y.; Hopfinger, A.J. Conformational analyses and molecular-shape comparisons of a series of indanone-benzylpiperidine inhibitors of acetylcholinesterase. J. Med. Chem., 1992, 35(3), 590-601.
[http://dx.doi.org/10.1021/jm00081a023] [PMID: 1738152]
Nordberg, A. Neuroreceptor changes in Alzheimer disease. Cerebrovasc. Brain Metab. Rev., 1992, 4(4), 303-328.
[PMID: 1486017]
Craig, L.A.; Hong, N.S.; McDonald, R.J. Revisiting the cholinergic hypothesis in the development of Alzheimer’s disease. Neurosci. Biobehav. Rev., 2011, 35(6), 1397-1409.
[http://dx.doi.org/10.1016/j.neubiorev.2011.03.001] [PMID: 21392524]
Fisher, A. Cholinergic treatments with emphasis on m1 muscarinic agonists as potential disease-modifying agents for Alzheimer’s disease. Neurotherapeutics, 2008, 5(3), 433-442.
[http://dx.doi.org/10.1016/j.nurt.2008.05.002] [PMID: 18625455]
Giacobini, E. Do cholinesterase inhibitors have disease-modifying effects in Alzheimer’s disease? CNS Drugs, 2001, 15(2), 85-91.
[http://dx.doi.org/10.2165/00023210-200115020-00001] [PMID: 11460892]
Kwon, K.J.; Kim, M.K.; Lee, E.J.; Kim, J.N.; Choi, B-R.; Kim, S.Y.; Cho, K.S.; Han, J-S.; Kim, H.Y.; Shin, C.Y.; Han, S-H. Effects of donepezil, an acetylcholinesterase inhibitor, on neurogenesis in a rat model of vascular dementia. J. Neurol. Sci., 2014, 347(1-2), 66-77.
[http://dx.doi.org/10.1016/j.jns.2014.09.021] [PMID: 25266713]
Giacobini, E. Selective inhibitors of butyrylcholinesterase: a valid alternative for therapy of Alzheimer’s disease? Drugs Aging, 2001, 18(12), 891-898.
[http://dx.doi.org/10.2165/00002512-200118120-00001] [PMID: 11888344]
Nordberg, A.; Ballard, C.; Bullock, R.; Darreh-Shori, T.; Somogyi, M. A review of butyrylcholinesterase as a therapeutic target in the treatment of Alzheimer’s disease. Prim. Care Companion CNS Disord., 2013, 15(2), 15.
[http://dx.doi.org/10.4088/PCC.12r01412] [PMID: 23930233]
Sheng, R.; Lin, X.; Li, J.; Jiang, Y.; Shang, Z.; Hu, Y. Design, synthesis, and evaluation of 2-phenoxy-indan-1-one derivatives as acetylcholinesterase inhibitors. Bioorg. Med. Chem. Lett., 2005, 15(17), 3834-3837.
[http://dx.doi.org/10.1016/j.bmcl.2005.05.132] [PMID: 15993600]
Shen, Y.; Sheng, R.; Zhang, J.; He, Q.; Yang, B.; Hu, Y. 2-Phenoxy-indan-1-one derivatives as acetylcholinesterase inhibitors: a study on the importance of modifications at the side chain on the activity. Bioorg. Med. Chem., 2008, 16(16), 7646-7653.
[http://dx.doi.org/10.1016/j.bmc.2008.07.014] [PMID: 18662884]
Ali, M.A.; Ismail, R.; Choon, T.S.; Yoon, Y.K.; Wei, A.C.; Pandian, S.; Kumar, R.S.; Osman, H.; Manogaran, E. Substituted spiro [2.3′] oxindolespiro [3.2″]-5,6-dimethoxy-indane-1″-one-pyrrolidine analogue as inhibitors of acetylcholinesterase. Bioorg. Med. Chem. Lett., 2010, 20(23), 7064-7066.
[http://dx.doi.org/10.1016/j.bmcl.2010.09.108] [PMID: 20951037]
Ashraf Ali, M.; Ismail, R.; Choon, T.S.; Kumar, R.S.; Osman, H.; Arumugam, N.; Almansour, A.I.; Elumalai, K.; Singh, A. AChE inhibitor: a regio- and stereo-selective 1,3-dipolar cycloaddition for the synthesis of novel substituted 5,6-dimethoxy spiro[5.3′]-oxindole-spiro-[6.3″]-2,3-dihydro-1H-inden-1″-one-7-(substituted aryl)-tetrahydro-1H-pyrrolo[1,2-c][1,3]thiazole.[1,2-c [1,3] Bioorg. Med. Chem. Lett., 2012, 22(1), 508-511.
[http://dx.doi.org/10.1016/j.bmcl.2011.10.087] [PMID: 22142546]
Nepovimova, E.; Korabecny, J.; Dolezal, R.; Babkova, K.; Ondrejicek, A.; Jun, D.; Sepsova, V.; Horova, A.; Hrabinova, M.; Soukup, O.; Bukum, N.; Jost, P.; Muckova, L.; Kassa, J.; Malinak, D.; Andrs, M.; Kuca, K. Tacrine-trolox hybrids: a novel class of centrally active, nonhepatotoxic multi-target-directed ligands exerting anticholinesterase and antioxidant activities with low in vivo toxicity. J. Med. Chem., 2015, 58(22), 8985-9003.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01325] [PMID: 26503905]
Sopkova-de Oliveira Santos, J.; Lesnard, A.; Agondanou, J-H.; Dupont, N.; Godard, A-M.; Stiebing, S.; Rochais, C.; Fabis, F.; Dallemagne, P.; Bureau, R.; Rault, S. Virtual screening discovery of new acetylcholinesterase inhibitors issued from CERMN chemical library. J. Chem. Inf. Model., 2010, 50(3), 422-428.
[http://dx.doi.org/10.1021/ci900491t] [PMID: 20196555]
Andreani, A.; Cavalli, A.; Granaiola, M.; Guardigli, M.; Leoni, A.; Locatelli, A.; Morigi, R.; Rambaldi, M.; Recanatini, M.; Roda, A. Synthesis and screening for antiacetylcholinesterase activity of (1-benzyl-4-oxopiperidin-3-ylidene)methylindoles and -pyrroles related to donepezil. J. Med. Chem., 2001, 44(23), 4011-4014.
[http://dx.doi.org/10.1021/jm0109356] [PMID: 11689088]
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]
Palin, R.; Clark, J.K.; Cowley, P.; Muir, A.W.; Pow, E.; Prosser, A.B.; Taylor, R.; Zhang, M-Q. Novel piperidinium and pyridinium agents as water-soluble acetylcholinesterase inhibitors for the reversal of neuromuscular blockade. Bioorg. Med. Chem. Lett., 2002, 12(18), 2569-2572.
[http://dx.doi.org/10.1016/S0960-894X(02)00483-3] [PMID: 12182862]
Zeng, F.; Jiang, H.; Zhai, Y.; Zhang, H.; Chen, K.; Ji, R. Synthesis and acetylcholinesterase inhibitory activity of huperzine A-E2020 combined compound. Bioorg. Med. Chem. Lett., 1999, 9(23), 3279-3284.
[http://dx.doi.org/10.1016/S0960-894X(99)00597-1] [PMID: 10612585]
Mezeiova, E.; Korabecny, J.; Sepsova, V.; Hrabinova, M.; Jost, P.; Muckova, L.; Kucera, T.; Dolezal, R.; Misik, J.; Spilovska, K.; Pham, N.L.; Pokrievkova, L.; Roh, J.; Jun, D.; Soukup, O.; Kaping, D.; Kuca, K. Development of 2-methoxyhuprine as novel lead for alzheimer’s disease therapy. Molecules, 2017, 22(8) pii: E1265
[http://dx.doi.org/10.3390/molecules22081265] [PMID: 28788095]
Shao, D.; Zou, C.; Luo, C.; Tang, X.; Li, Y. Synthesis and evaluation of tacrine-E2020 hybrids as acetylcholinesterase inhibitors for the treatment of Alzheimer’s disease. Bioorg. Med. Chem. Lett., 2004, 14(18), 4639-4642.
[http://dx.doi.org/10.1016/j.bmcl.2004.07.005] [PMID: 15324879]
Mantoani, S.P.; Chierrito, T.P.C.; Vilela, A.F.L.; Cardoso, C.L.; Martínez, A.; Carvalho, I. Novel triazole-quinoline derivatives as selective dual binding site acetylcholinesterase inhibitors. Molecules, 2016, 21(2), 193.
[http://dx.doi.org/10.3390/molecules21020193] [PMID: 26861273]
Villalobos, A.; Blake, J.F.; Biggers, C.K.; Butler, T.W.; Chapin, D.S.; Chen, Y.L.; Ives, J.L.; Jones, S.B.; Liston, D.R.; Nagel, A.A. Novel benzisoxazole derivatives as potent and selective inhibitors of acetylcholinesterase. J. Med. Chem., 1994, 37(17), 2721-2734.
[http://dx.doi.org/10.1021/jm00043a012] [PMID: 8064800]
Omran, Z.; Cailly, T.; Lescot, E.; Santos, J.S.O.; Agondanou, J-H.; Lisowski, V.; Fabis, F.; Godard, A-M.; Stiebing, S.; Le Flem, G.; Boulouard, M.; Dauphin, F.; Dallemagne, P.; Rault, S. Synthesis and biological evaluation as AChE inhibitors of new indanones and thiaindanones related to donepezil. Eur. J. Med. Chem., 2005, 40(12), 1222-1245.
[http://dx.doi.org/10.1016/j.ejmech.2005.07.009] [PMID: 16137794]
Omran, Z.; Stiebing, S.; Godard, A-M.; Sopkova-De Oliveira-Santos, J.; Dallemagne, P. Synthesis and biological evaluation of new donepezil-like Thiaindanones as AChE inhibitors. J. Enzyme Inhib. Med. Chem., 2008, 23(5), 696-703.
[http://dx.doi.org/10.1080/14756360802208053] [PMID: 18821258]
Ono, M.; Haratake, M.; Mori, H.; Nakayama, M. Novel chalcones as probes for in vivo imaging of beta-amyloid plaques in Alzheimer’s brains. Bioorg. Med. Chem., 2007, 15(21), 6802-6809.
[http://dx.doi.org/10.1016/j.bmc.2007.07.052] [PMID: 17826102]
Ono, M.; Maya, Y.; Haratake, M.; Ito, K.; Mori, H.; Nakayama, M. Aurones serve as probes of beta-amyloid plaques in Alzheimer’s disease. Biochem. Biophys. Res. Commun., 2007, 361(1), 116-121.
[http://dx.doi.org/10.1016/j.bbrc.2007.06.162] [PMID: 17644062]
Sheng, R.; Xu, Y.; Hu, C.; Zhang, J.; Lin, X.; Li, J.; Yang, B.; He, Q.; Hu, Y. Design, synthesis and AChE inhibitory activity of indanone and aurone derivatives. Eur. J. Med. Chem., 2009, 44(1), 7-17.
[http://dx.doi.org/10.1016/j.ejmech.2008.03.003] [PMID: 18436348]
Sheng, R.; Lin, X.; Zhang, J.; Chol, K.S.; Huang, W.; Yang, B.; He, Q.; Hu, Y. Design, synthesis and evaluation of flavonoid derivatives as potent AChE inhibitors. Bioorg. Med. Chem., 2009, 17(18), 6692-6698.
[http://dx.doi.org/10.1016/j.bmc.2009.07.072] [PMID: 19692250]
Kim, H.; Park, B-S.; Lee, K-G.; Choi, C.Y.; Jang, S.S.; Kim, Y-H.; Lee, S-E. Effects of naturally occurring compounds on fibril formation and oxidative stress of beta-amyloid. J. Agric. Food Chem., 2005, 53(22), 8537-8541.
[http://dx.doi.org/10.1021/jf051985c] [PMID: 16248550]
Wang, C.N.; Chi, C.W.; Lin, Y.L.; Chen, C.F.; Shiao, Y.J. The neuroprotective effects of phytoestrogens on amyloid beta protein-induced toxicity are mediated by abrogating the activation of caspase cascade in rat cortical neurons. J. Biol. Chem., 2001, 276(7), 5287-5295.
[http://dx.doi.org/10.1074/jbc.M006406200] [PMID: 11083861]
Zhu, J.T.T.; Choi, R.C.Y.; Chu, G.K.Y.; Cheung, A.W.H.; Gao, Q.T.; Li, J.; Jiang, Z.Y.; Dong, T.T.X.; Tsim, K.W.K. Flavonoids possess neuroprotective effects on cultured pheochromocytoma PC12 cells: a comparison of different flavonoids in activating estrogenic effect and in preventing beta-amyloid-induced cell death. J. Agric. Food Chem., 2007, 55(6), 2438-2445.
[http://dx.doi.org/10.1021/jf063299z] [PMID: 17323972]
Shen, Y.; Zhang, J.; Sheng, R.; Dong, X.; He, Q.; Yang, B.; Hu, Y. Synthesis and biological evaluation of novel flavonoid derivatives as dual binding acetylcholinesterase inhibitors. J. Enzyme Inhib. Med. Chem., 2009, 24(2), 372-380.
[http://dx.doi.org/10.1080/14756360802187885] [PMID: 18830885]
Chaudhaery, S.S.; Roy, K.K.; Shakya, N.; Saxena, G.; Sammi, S.R.; Nazir, A.; Nath, C.; Saxena, A.K. Novel carbamates as orally active acetylcholinesterase inhibitors found to improve scopolamine-induced cognition impairment: pharmacophore-based virtual screening, synthesis, and pharmacology. J. Med. Chem., 2010, 53(17), 6490-6505.
[http://dx.doi.org/10.1021/jm100573q] [PMID: 20684567]
Roy, K.K.; Tota, S.; Tripathi, T.; Chander, S.; Nath, C.; Saxena, A.K. Lead optimization studies towards the discovery of novel carbamates as potent AChE inhibitors for the potential treatment of Alzheimer’s disease. Bioorg. Med. Chem., 2012, 20(21), 6313-6320.
[http://dx.doi.org/10.1016/j.bmc.2012.09.005] [PMID: 23026084]
Tormos, J.R.; Wiley, K.L.; Wang, Y.; Fournier, D.; Masson, P.; Nachon, F.; Quinn, D.M. Accumulation of tetrahedral intermediates in cholinesterase catalysis: a secondary isotope effect study. J. Am. Chem. Soc., 2010, 132(50), 17751-17759.
[http://dx.doi.org/10.1021/ja104496q] [PMID: 21105647]
Contreras, J.M.; Rival, Y.M.; Chayer, S.; Bourguignon, J.J.; Wermuth, C.G. Aminopyridazines as acetylcholinesterase inhibitors. J. Med. Chem., 1999, 42(4), 730-741.
[http://dx.doi.org/10.1021/jm981101z] [PMID: 10052979]
Garattini, S.; Forloni, G.L.; Tirelli, S.; Ladinsky, H.; Consolo, S. Neurochemical effects of minaprine, a novel psychotropic drug, on the central cholinergic system of the rat. Psychopharmacology (Berl.), 1984, 82(3), 210-214.
[http://dx.doi.org/10.1007/BF00427775] [PMID: 6425901]
Contreras, J.M.; Parrot, I.; Sippl, W.; Rival, Y.M.; Wermuth, C.G. Design, synthesis, and structure-activity relationships of a series of 3-[2-(1-benzylpiperidin-4-yl)ethylamino]pyridazine derivatives as acetylcholinesterase inhibitors. J. Med. Chem., 2001, 44(17), 2707-2718.
[http://dx.doi.org/10.1021/jm001088u] [PMID: 11495583]
Szymański, P.; Janik, A.; Zurek, E.; Mikiciuk-Olasik, E. Design, synthesis and biological evaluation of new 2-benzoxazolinone derivatives as potential cholinesterase inhibitors for therapy of alzheimer’s disease. Pharmazie, 2011, 66(6), 399-403.
[http://dx.doi.org/10.1002/chin.201134123] [PMID: 21699076]
Szymański, P.; Markowicz, M.; Mikiciuk-Olasik, E. Synthesis and biological activity of derivatives of tetrahydroacridine as acetylcholinesterase inhibitors. Bioorg. Chem., 2011, 39(4), 138-142.
[http://dx.doi.org/10.1016/j.bioorg.2011.05.001] [PMID: 21621811]
Zurek, E.; Szymański, P.; Mikiciuk-Olasik, E. Synthesis and biological activity of new donepezil-hydrazinonicotinamide hybrids. Drug Res. (Stuttg.), 2013, 63(3), 137-144.
[http://dx.doi.org/10.1055/s-0033-1333735] [PMID: 23447117]
Meszaros, L.K.; Dose, A.; Biagini, S.C.G.; Blower, P.J. Synthesis and evaluation of analogues of HYNIC as bifunctional chelators for technetium. Dalton Trans., 2011, 40(23), 6260-6267.
[http://dx.doi.org/10.1039/c0dt01608j] [PMID: 21350776]
Ha, G.T.; Wong, R.K.; Zhang, Y. Huperzine a as potential treatment of Alzheimer’s disease: an assessment on chemistry, pharmacology, and clinical studies. Chem. Biodivers., 2011, 8(7), 1189-1204.
[http://dx.doi.org/10.1002/cbdv.201000269] [PMID: 21766442]
Hu, Y.; Zhang, J.; Chandrashankra, O.; Ip, F.C.F.; Ip, N.Y. Design, synthesis and evaluation of novel heterodimers of donepezil and huperzine fragments as acetylcholinesterase inhibitors. Bioorg. Med. Chem., 2013, 21(3), 676-683.
[http://dx.doi.org/10.1016/j.bmc.2012.11.044] [PMID: 23273608]
Yue, J.; Dong, B.R.; Lin, X.; Yang, M.; Wu, H.M.; Wu, T. Huperzine A for mild cognitive impairment. Cochrane Database Syst. Rev., 2012, 12CD008827
[http://dx.doi.org/10.1002/14651858.CD008827.pub2] [PMID: 23235666]
Ismail, M.M.; Kamel, M.M.; Mohamed, L.W.; Faggal, S.I. Synthesis of new indole derivatives structurally related to donepezil and their biological evaluation as acetylcholinesterase inhibitors. Molecules, 2012, 17(5), 4811-4823.
[http://dx.doi.org/10.3390/molecules17054811] [PMID: 22534665]
Ismail, M.M.; Kamel, M.M.; Mohamed, L.W.; Faggal, S.I.; Galal, M.A. Synthesis and biological evaluation of thiophene derivatives as acetylcholinesterase inhibitors. Molecules, 2012, 17(6), 7217-7231.
[http://dx.doi.org/10.3390/molecules17067217] [PMID: 22692245]
Liew, K-F.; Chan, K-L.; Lee, C-Y. Blood-brain barrier permeable anticholinesterase aurones: synthesis, structure-activity relationship, and drug-like properties. Eur. J. Med. Chem., 2015, 94, 195-210.
[http://dx.doi.org/10.1016/j.ejmech.2015.02.055] [PMID: 25768702]
Mohammadi-Farani, A.; Abdi, N.; Moradi, A.; Aliabadi, A. 2-(2-(4-Benzoylpiperazin-1-yl)ethyl)isoindoline-1,3-dione derivatives: Synthesis, docking and acetylcholinesterase inhibitory evaluation as anti-alzheimer agents. Iran. J. Basic Med. Sci., 2017, 20(1), 59-66.
[PMID: 28133526]
Mostofi, M.; Mohammadi Ziarani, G.; Mahdavi, M.; Moradi, A.; Nadri, H.; Emami, S.; Alinezhad, H.; Foroumadi, A.; Shafiee, A. Synthesis and structure-activity relationship study of benzofuran-based chalconoids bearing benzylpyridinium moiety as potent acetylcholinesterase inhibitors. Eur. J. Med. Chem., 2015, 103, 361-369.
[http://dx.doi.org/10.1016/j.ejmech.2015.08.061] [PMID: 26363872]
van Greunen, D.G.; Cordier, W.; Nell, M.; van der Westhuyzen, C.; Steenkamp, V.; Panayides, J-L.; Riley, D.L. Targeting Alzheimer’s disease by investigating previously unexplored chemical space surrounding the cholinesterase inhibitor donepezil. Eur. J. Med. Chem., 2017, 127, 671-690.
[http://dx.doi.org/10.1016/j.ejmech.2016.10.036] [PMID: 27823887]
Sağlık, B.N.; Ilgın, S.; Özkay, Y. Synthesis of new donepezil analogues and investigation of their effects on cholinesterase enzymes. Eur. J. Med. Chem., 2016, 124, 1026-1040.
[http://dx.doi.org/10.1016/j.ejmech.2016.10.042] [PMID: 27783974]
Nishijo, J.; Yonetani, I.; Iwamoto, E.; Tokura, S.; Tagahara, K.; Sugiura, M. Interaction of caffeine with L-tryptophan: study by 1H nuclear magnetic resonance spectroscopy. J. Pharm. Sci., 1990, 79(1), 14-18.
[http://dx.doi.org/10.1002/jps.2600790105] [PMID: 2313569]
Rodríguez-Franco, M.I.; Fernández-Bachiller, M.I.; Pérez, C.; Castro, A.; Martínez, A. Design and synthesis of N-benzylpiperidine-purine derivatives as new dual inhibitors of acetyl- and butyrylcholinesterase. Bioorg. Med. Chem., 2005, 13(24), 6795-6802.
[http://dx.doi.org/10.1016/j.bmc.2005.07.019] [PMID: 16183292]
Korabecny, J.; Dolezal, R.; Cabelova, P.; Horova, A.; Hruba, E.; Ricny, J.; Sedlacek, L.; Nepovimova, E.; Spilovska, K.; Andrs, M.; Musilek, K.; Opletalova, V.; Sepsova, V.; Ripova, D.; Kuca, K. 7-MEOTA-donepezil like compounds as cholinesterase inhibitors: Synthesis, pharmacological evaluation, molecular modeling and QSAR studies. Eur. J. Med. Chem., 2014, 82, 426-438.
[http://dx.doi.org/10.1016/j.ejmech.2014.05.066] [PMID: 24929293]
Sepsova, V.; Karasova, J.Z.; Tobin, G.; Jun, D.; Korabecny, J.; Cabelova, P.; Janska, K.; Krusek, J.; Skrenkova, K.; Kuca, K.; Soukup, O. Cholinergic properties of new 7-methoxytacrine-donepezil derivatives. Gen. Physiol. Biophys., 2015, 34(2), 189-200.
[http://dx.doi.org/10.4149/gpb_2014036] [PMID: 25504063]
Korabecny, J.; Musilek, K.; Zemek, F.; Horova, A.; Holas, O.; Nepovimova, E.; Opletalova, V.; Hroudova, J.; Fisar, Z.; Jung, Y-S.; Kuca, K. Synthesis and in vitro evaluation of 7-methoxy-N-(pent-4-enyl)-1,2,3,4-tetrahydroacridin-9-amine-new tacrine derivate with cholinergic properties. Bioorg. Med. Chem. Lett., 2011, 21(21), 6563-6566.
[http://dx.doi.org/10.1016/j.bmcl.2011.08.042] [PMID: 21920739]
Korabecny, J.; Musilek, K.; Holas, O.; Binder, J.; Zemek, F.; Marek, J.; Pohanka, M.; Opletalova, V.; Dohnal, V.; Kuca, K. Synthesis and in vitro evaluation of N-alkyl-7-methoxytacrine hydrochlorides as potential cholinesterase inhibitors in Alzheimer disease. Bioorg. Med. Chem. Lett., 2010, 20(20), 6093-6095.
[http://dx.doi.org/10.1016/j.bmcl.2010.08.044] [PMID: 20817518]
Korabecny, J.; Musilek, K.; Holas, O.; Nepovimova, E.; Jun, D.; Zemek, F.; Opletalova, V.; Patocka, J.; Dohnal, V.; Nachon, F.; Hroudova, J.; Fisar, Z.; Kuca, K. Synthesis and in vitro evaluation of N-(Bromobut-3-en-2-yl)-7-methoxy-1,2,3,4-tetrahydroacridin-9-amine as a cholinesterase inhibitor with regard to Alzheimer’s disease treatment. Molecules, 2010, 15(12), 8804-8812.
[http://dx.doi.org/10.3390/molecules15128804] [PMID: 21127466]
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]
Spilovska, K.; Korabecny, J.; Horova, A.; Musilek, K.; Nepovimova, E.; Drtinova, L.; Gazova, Z.; Siposova, K.; Dolezal, R.; Jun, D.; Kuca, K. Design, Synthesis and in vitro testing of 7-methoxytacrine-amantadine analogues: a novel cholinesterase inhibitors for the treatment of Alzheimer’s disease. Med. Chem. Res., 2015, 1-11.
Spilovska, K.; Korabecny, J.; Kral, J.; Horova, A.; Musilek, K.; Soukup, O.; Drtinova, L.; Gazova, Z.; Siposova, K.; Kuca, K. 7-Methoxytacrine-adamantylamine heterodimers as cholinesterase inhibitors in Alzheimer’s disease treatment--synthesis, biological evaluation and molecular modeling studies. Molecules, 2013, 18(2), 2397-2418.
[http://dx.doi.org/10.3390/molecules18022397] [PMID: 23429378]
Korabecny, J.; Holas, O.; Musilek, K.; Pohanka, M.; Opletalova, V.; Dohnal, V.; Kuca, K. Synthesis and in vitro evaluation of new tacrine derivates-bis-alkylene linked 7-MEOTA. Lett. Org. Chem., 2010, 7, 327-331.
Gazova, Z.; Soukup, O.; Sepsova, V.; Siposova, K.; Drtinova, L.; Jost, P.; Spilovska, K.; Korabecny, J.; Nepovimova, E.; Fedunova, D.; Horak, M.; Kaniakova, M.; Wang, Z-J.; Hamouda, A.K.; Kuca, K. Multi-target-directed therapeutic potential of 7-methoxytacrine-adamantylamine heterodimers in the Alzheimer’s disease treatment. Biochim. Biophys. Acta Mol. Basis Dis., 2017, 1863(2), 607-619.
[http://dx.doi.org/10.1016/j.bbadis.2016.11.020] [PMID: 27865910]
Korabecny, J.; Janovec, L.; Musilek, K.; Zemek, F.; Horova, A.; Nepovimova, E.; Dolezal, R.; Opletalova, V.; Hroudova, J.; Fisar, Z.; Jung, Y-S.; Kuca, K. Comparison of novel tacrine and 7-MEOTA derivatives with aromatic and alicyclic residues: synthesis, biological evaluation and docking studies. Lett. Org. Chem., 2013, 10, 291-297.
Lee, S.K.; Park, M.K.; Jhang, H.E.; Yi, J.; Nahm, K.; Cho, D.W.; Ra, C.S.; Musilek, K.; Horova, A.; Korabecny, J.; Dolezal, R.; Jun, D.; Kuca, K. Preparation of 7-methoxy tacrine dimer analogs and their in vitro/in silico evaluation as potential cholinesterase inhibitors. Bull. Korean Chem. Soc., 2015, 36, 1654-1660.
Rydberg, E.H.; Brumshtein, B.; Greenblatt, H.M.; Wong, D.M.; Shaya, D.; Williams, L.D.; Carlier, P.R.; Pang, Y-P.; Silman, I.; Sussman, J.L. Complexes of alkylene-linked tacrine dimers with Torpedo californica acetylcholinesterase: Binding of Bis5-tacrine produces a dramatic rearrangement in the active-site gorge. J. Med. Chem., 2006, 49(18), 5491-5500.
[http://dx.doi.org/10.1021/jm060164b] [PMID: 16942022]
Misik, J.; Korabecny, J.; Nepovimova, E.; Kracmarova, A.; Kassa, J. Effects of novel tacrine-related cholinesterase inhibitors in the reversal of 3-quinuclidinyl benzilate-induced cognitive deficit in rats--Is there a potential for Alzheimer’s disease treatment? Neurosci. Lett., 2016, 612, 261-268.
[http://dx.doi.org/10.1016/j.neulet.2015.12.021] [PMID: 26708634]
Misik, J.; Korabecny, J.; Nepovimova, E.; Cabelova, P.; Kassa, J. The effects of novel 7-MEOTA-donepezil like hybrids and N-alkylated tacrine analogues in the treatment of quinuclidinyl benzilate-induced behavioural deficits in rats performing the multiple T-maze test. Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech Repub., 2015, 159(4), 547-553.
[http://dx.doi.org/10.5507/bp.2015.006] [PMID: 25690521]
Mzik, M.; Korabecny, J.; Nepovimova, E.; Voříšek, V.; Palička, V.; Kuca, K.; Zdarova Karasova, J. An HPLC-MS method for the quantification of new acetylcholinesterase inhibitor PC 48 (7-MEOTA-donepezil like compound) in rat plasma: Application to a pharmacokinetic study. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2016, 1020, 85-89.
[http://dx.doi.org/10.1016/j.jchromb.2016.02.038] [PMID: 27030895]
Korabecny, J.; Andrs, M.; Nepovimova, E.; Dolezal, R.; Babkova, K.; Horova, A.; Malinak, D.; Mezeiova, E.; Gorecki, L.; Sepsova, V.; Hrabinova, M.; Soukup, O.; Jun, D.; Kuca, K. 7-Methoxytacrine-p-anisidine hybrids as novel dual binding site acetylcholinesterase inhibitors for alzheimer’s disease treatment. Molecules, 2015, 20(12), 22084-22101.
[http://dx.doi.org/10.3390/molecules201219836] [PMID: 26690394]
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]
Korábečný, J.; Nepovimová, E.; Cikánková, T.; Špilovská, K.; Vašková, L.; Mezeiová, E.; Kuča, K.; Hroudová, J. Newly developed drugs for alzheimer’s disease in relation to energy metabolism, cholinergic and monoaminergic neurotransmission. Neuroscience, 2018, 370, 191-206.
[http://dx.doi.org/10.1016/j.neuroscience.2017.06.034] [PMID: 28673719]
Prati, F.; Bergamini, C.; Fato, R.; Soukup, O.; Korabecny, J.; Andrisano, V.; Bartolini, M.; Bolognesi, M.L. Novel 8-hydroxyquinoline derivatives as multitarget compounds for the treatment of alzheimer’s disease. ChemMedChem, 2016, 11(12), 1284-1295.
[http://dx.doi.org/10.1002/cmdc.201600014] [PMID: 26880501]

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Year: 2019
Page: [5625 - 5648]
Pages: 24
DOI: 10.2174/0929867325666180517094023
Price: $65

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