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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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Review Article

A Recent Appraisal of Small-Organic Molecules as Anti-Alzheimer’s Agents

Author(s): Mohan Gupta, Avinash Kumar, Madhwi Ojha, Shabana Kausar Khan and Sumitra Nain*

Volume 23, Issue 8, 2023

Published on: 21 October, 2022

Page: [962 - 976] Pages: 15

DOI: 10.2174/1389557522666220922105934

Price: $65

Abstract

Background: Alzheimer’s disease (AD) is an irreversible, progressive and very complex brain disorder. There is still uncertainty about the etiology of AD; however, a few hallmarks like an aggregation of tau proteins, amyloid-β plaques, oxidative stress, low level of choline in the brain etc., play significant roles.

Objective: In the present work, we aim to evaluate the recent progress in the development of small organic molecules containing heterocycles like thiazole, pyridines, dihydropyridines, piperidines, pyrrolidines, pyrazoles, quinolines etc. as anti-Alzheimer’s agents.

Methods: Several databases, including SciFinder, ScienceDirect, Bentham Science, and PubMed, were searched for relevant articles and reviewed for the present work.

Results: Several research groups are actively working on these heterocycle-based compounds as potent single-target inhibitors. Most of the analogues have been evaluated for their cholinesterase (acetylcholinesterase and butyrylcholinesterase) inhibition potential. Several studies have also reported the inhibitory potential of the analogues against MAO-A, MAO-B, and BACE-1 enzymes. However, instead of targeting one enzyme or protein, more than one heterocycle ring is being joined to develop MTDLs (multi-target-directed ligands). Donepezil has become the focal point of anti-AD drug discovery projects. Several research groups have reported various donepezil-based analogues by replacing/ modifying its various ring systems like indanone, piperidine or the methylene linker.

Conclusion: Small molecules with nitrogen-containing heterocycles have become the core of drug discovery efforts for AD. With the increasing prominence of the MTDL approach, several new ligands are being discovered as potent anti-AD agents.

Keywords: Acetylcholinesterase inhibitors, Brain disorders, Dementia, Donepezil, β-secretase inhibitors, Neurodegeneration

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[1]
Hippius, H.; Neundörfer, G. The discovery of Alzheimer’s disease. Dialogues Clin. Neurosci., 2003, 5(1), 101-108.
[http://dx.doi.org/10.31887/DCNS.2003.5.1/hhippius] [PMID: 22034141]
[2]
Breijyeh, Z.; Karaman, R.; Muñoz-Torrero, D.; Dembinski, R. Comprehensive review on Alzheimer’s disease: Causes and treatment. Molecules, 2020, 25(24), 5789.
[http://dx.doi.org/10.3390/molecules25245789] [PMID: 33302541]
[3]
De-Paula, V.J.; Radanovic, M.; Diniz, B.S.; Forlenza, O.V.; Forlenza, O.V.; De-Paula, V.J. Alzheimer’s disease. Subcell. Biochem., 2012, 65, 329-352.
[http://dx.doi.org/10.1007/978-94-007-5416-4_14] [PMID: 23225010]
[4]
Livingston, G.; Huntley, J.; Sommerlad, A.; Ames, D.; Ballard, C.; Banerjee, S.; Brayne, C.; Burns, A.; Cohen-Mansfield, J.; Cooper, C.; Costafreda, S.G.; Dias, A.; Fox, N.; Gitlin, L.N.; Howard, R.; Kales, H.C.; Kivimäki, M.; Larson, E.B.; Ogunniyi, A.; Orgeta, V.; Ritchie, K.; Rockwood, K.; Sampson, E.L.; Samus, Q.; Schneider, L.S.; Selbæk, G.; Teri, L.; Mukadam, N. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet, 2020, 396(10248), 413-446.
[http://dx.doi.org/10.1016/S0140-6736(20)30367-6] [PMID: 32738937]
[5]
Singh, S.K.; Srivastav, S.; Yadav, A.K.; Srikrishna, S.; Perry, G. Overview of Alzheimer’s disease and some therapeutic approaches targeting Aβ by using several synthetic and herbal compounds. Oxid. Med. Cell. Longev., 2016, 2016, 7361613.
[6]
Spires-Jones, T.L.; Hyman, B.T. The intersection of amyloid beta and tau at synapses in Alzheimer’s disease. Neuron, 2014, 82(4), 756-771.
[http://dx.doi.org/10.1016/j.neuron.2014.05.004] [PMID: 24853936]
[7]
Serrano-Pozo, A.; Frosch, M.P.; Masliah, E.; Hyman, B.T. Neuropathological alterations in Alzheimer disease. Cold Spring Harb. Perspect. Med., 2011, 1(1), a006189.
[http://dx.doi.org/10.1101/cshperspect.a006189] [PMID: 22229116]
[8]
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]
[9]
Crismon, M.L. Tacrine: first drug approved for Alzheimer’s disease. Ann. Pharmacother., 1994, 28(6), 744-751.
[http://dx.doi.org/10.1177/106002809402800612] [PMID: 7919566]
[10]
Qizilbash, N.; Birks, J.; López Arrieta, J.; Lewington, S.; Szeto, S. Tacrine for Alzheimer’s disease. Cochrane Database Syst. Rev., 2000, 3, CD000202.
[11]
Kerru, N.; Gummidi, L.; Maddila, S.; Gangu, K.K.; Jonnalagadda, S.B. A review on recent advances in nitrogen-containing molecules and their biological applications. Molecules, 2020, 25(8), 1909.
[http://dx.doi.org/10.3390/molecules25081909] [PMID: 32326131]
[12]
Vitaku, E.; Smith, D.T.; Njardarson, J.T. Analysis of the structural diversity, substitution patterns, and frequency of nitrogen heterocycles among U.S. FDA approved pharmaceuticals. J. Med. Chem., 2014, 57(24), 10257-10274.
[http://dx.doi.org/10.1021/jm501100b] [PMID: 25255204]
[13]
Mermer, A.; Keles, T.; Sirin, Y. Recent studies of nitrogen containing heterocyclic compounds as novel antiviral agents: A review. Bioorg. Chem., 2021, 114, 105076.
[http://dx.doi.org/10.1016/j.bioorg.2021.105076] [PMID: 34157555]
[14]
Hosseinzadeh, Z.; Ramazani, A.; Razzaghi-Asl, N. Anti-cancer nitrogen-containing heterocyclic compounds. Curr. Org. Chem., 2018, 22(23), 2256-2279.
[http://dx.doi.org/10.2174/1385272822666181008142138]
[15]
Kurt, B.Z.; Gazioglu, I.; Basile, L.; Sonmez, F.; Ginex, T.; Kucukislamoglu, M.; Guccione, S. Potential of aryl-urea-benzofuranylthiazoles hybrids as multitasking agents in Alzheimer’s disease. Eur. J. Med. Chem., 2015, 102, 80-92.
[http://dx.doi.org/10.1016/j.ejmech.2015.07.005] [PMID: 26244990]
[16]
Kurt, B.Z.; Gazioglu, I.; Sonmez, F.; Kucukislamoglu, M. Synthesis, antioxidant and anticholinesterase activities of novel coumarylthiazole derivatives. Bioorg. Chem., 2015, 59, 80-90.
[http://dx.doi.org/10.1016/j.bioorg.2015.02.002] [PMID: 25706320]
[17]
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]
[18]
Shidore, M.; Machhi, J.; Shingala, K.; Murumkar, P.; Sharma, M.K.; Agrawal, N.; Tripathi, A.; Parikh, Z.; Pillai, P.; Yadav, M.R. Benzylpiperidine-linked diarylthiazoles as potential anti-alzheimer’s agents: Synthesis and biological evaluation. J. Med. Chem., 2016, 59(12), 5823-5846.
[http://dx.doi.org/10.1021/acs.jmedchem.6b00426] [PMID: 27253679]
[19]
O’Neill, B.T.; Beck, E.M.; Butler, C.R.; Nolan, C.E.; Gonzales, C.; Zhang, L.; Doran, S.D.; Lapham, K.; Buzon, L.M.; Dutra, J.K.; Barreiro, G.; Hou, X.; Martinez-Alsina, L.A.; Rogers, B.N.; Villalobos, A.; Murray, J.C.; Ogilvie, K.; LaChapelle, E.A.; Chang, C.; Lanyon, L.F.; Steppan, C.M.; Robshaw, A.; Hales, K.; Boucher, G.G.; Pandher, K.; Houle, C.; Ambroise, C.W.; Karanian, D.; Riddell, D.; Bales, K.R.; Brodney, M.A. Design and synthesis of clinical candidate PF-06751979: A potent, brain penetrant, β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor lacking hypopigmentation. J. Med. Chem., 2018, 61(10), 4476-4504.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00246] [PMID: 29613789]
[20]
Hemaida, A.Y.; Hassan, G.S.; Maarouf, A.R.; Joubert, J.; El-Emam, A.A. Synthesis and biological evaluation of thiazole-based derivatives as potential acetylcholinesterase inhibitors. ACS Omega, 2021, 6(29), 19202-19211.
[http://dx.doi.org/10.1021/acsomega.1c02549] [PMID: 34337258]
[21]
Pandya, D.H.; Sharma, J.A.; Jalani, H.B.; Pandya, A.N.; Sudarsanam, V.; Kachler, S.; Klotz, K.N.; Vasu, K.K. Novel thiazole–thiophene conjugates as adenosine receptor antagonists: Synthesis, biological evaluation and docking studies. Bioorg. Med. Chem. Lett., 2015, 25(6), 1306-1309.
[http://dx.doi.org/10.1016/j.bmcl.2015.01.040] [PMID: 25686851]
[22]
Durães, F.; Pinto, M.; Sousa, E. Old drugs as new treatments for neurodegenerative diseases. Pharmaceuticals (Basel), 2018, 11(2), 44.
[http://dx.doi.org/10.3390/ph11020044] [PMID: 29751602]
[23]
Netzer, W.J.; Dou, F.; Cai, D.; Veach, D.; Jean, S.; Li, Y.; Bornmann, W.G.; Clarkson, B.; Xu, H.; Greengard, P. Gleevec inhibits β-amyloid production but not Notch cleavage. Proc. Natl. Acad. Sci. USA, 2003, 100(21), 12444-12449.
[http://dx.doi.org/10.1073/pnas.1534745100] [PMID: 14523244]
[24]
Grossi, C.; Francese, S.; Casini, A.; Rosi, M.C.; Luccarini, I.; Fiorentini, A.; Gabbiani, C.; Messori, L.; Moneti, G.; Casamenti, F. Clioquinol decreases amyloid-beta burden and reduces working memory impairment in a transgenic mouse model of Alzheimer’s disease. J. Alzheimers Dis., 2009, 17(2), 423-440.
[http://dx.doi.org/10.3233/JAD-2009-1063] [PMID: 19363260]
[25]
de Jong, D.L.K.; de Heus, R.A.A.; Rijpma, A.; Donders, R.; Olde Rikkert, M.G.M.; Günther, M.; Lawlor, B.A.; van Osch, M.J.P.; Claassen, J.A.H.R. Effects of nilvadipine on cerebral blood flow in patients with Alzheimer disease. Hypertension, 2019, 74(2), 413-420.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.12892] [PMID: 31203725]
[26]
Bachmeier, C.; Beaulieu-Abdelahad, D.; Mullan, M.; Paris, D. Selective dihydropyiridine compounds facilitate the clearance of β-amyloid across the blood-brain barrier. Eur. J. Pharmacol., 2011, 659(2-3), 124-129.
[http://dx.doi.org/10.1016/j.ejphar.2011.03.048] [PMID: 21497592]
[27]
Zhao, W.; Wang, J.; Ho, L.; Ono, K.; Teplow, D.B.; Pasinetti, G.M. Identification of antihypertensive drugs which inhibit amyloid-beta protein oligomerization. J. Alzheimers Dis., 2009, 16(1), 49-57.
[http://dx.doi.org/10.3233/JAD-2009-0925] [PMID: 19158421]
[28]
Leoni, A.; Frosini, M.; Locatelli, A.; Micucci, M.; Carotenuto, C.; Durante, M.; Cosconati, S.; Budriesi, R. 4-Imidazo[2,1-b]thiazole-1,4-DHPs and neuroprotection: Preliminary study in hits searching. Eur. J. Med. Chem., 2019, 169, 89-102.
[http://dx.doi.org/10.1016/j.ejmech.2019.02.075] [PMID: 30861492]
[29]
Bai, D.L.; Tang, X.C.; He, X.C. Huperzine A, a potential therapeutic agent for treatment of Alzheimer’s disease. Curr. Med. Chem., 2000, 7(3), 355-374.
[http://dx.doi.org/10.2174/0929867003375281] [PMID: 10637369]
[30]
Umar, T.; Shalini, S.; Raza, M.K.; Gusain, S.; Kumar, J.; Seth, P.; Tiwari, M.; Hoda, N. A multifunctional therapeutic approach: Synthesis, biological evaluation, crystal structure and molecular docking of diversified 1H-pyrazolo[3,4-b]pyridine derivatives against Alzheimer’s disease. Eur. J. Med. Chem., 2019, 175, 2-19.
[http://dx.doi.org/10.1016/j.ejmech.2019.04.038] [PMID: 31055149]
[31]
Haghighijoo, Z.; Akrami, S.; Saeedi, M.; Zonouzi, A.; Iraji, A.; Larijani, B.; Fakherzadeh, H.; Sharifi, F.; Arzaghi, S.M.; Mahdavi, M.; Edraki, N. N-Cyclohexylimidazo[1,2-a]pyridine derivatives as multi-target-directed ligands for treatment of Alzheimer’s disease. Bioorg. Chem., 2020, 103, 104146.
[http://dx.doi.org/10.1016/j.bioorg.2020.104146] [PMID: 32777579]
[32]
Nirogi, R.; Mohammed, A.R.; Shinde, A.K.; Bogaraju, N.; Gagginapalli, S.R.; Ravella, S.R.; Kota, L.; Bhyrapuneni, G.; Muddana, N.R.; Benade, V.; Palacharla, R.C.; Jayarajan, P.; Subramanian, R.; Goyal, V.K. Synthesis and SAR of Imidazo[1,5-a]pyridine derivatives as 5-HT4 receptor partial agonists for the treatment of cognitive disorders associated with Alzheimer’s disease. Eur. J. Med. Chem., 2015, 103, 289-301.
[http://dx.doi.org/10.1016/j.ejmech.2015.08.051] [PMID: 26363507]
[33]
Saeedi, M.; Safavi, M.; Allahabadi, E.; Rastegari, A.; Hariri, R.; Jafari, S.; Bukhari, S.N.A.; Mirfazli, S.S.; Firuzi, O.; Edraki, N.; Mahdavi, M.; Akbarzadeh, T. Thieno[2,3‐ b]pyridine amines: Synthesis and evaluation of tacrine analogs against biological activities related to Alzheimer’s disease. Arch. Pharm. (Weinheim), 2020, 353(10), 2000101.
[http://dx.doi.org/10.1002/ardp.202000101] [PMID: 32657467]
[34]
Li, X.; Wang, H.; Lu, Z.; Zheng, X.; Ni, W.; Zhu, J.; Fu, Y.; Lian, F.; Zhang, N.; Li, J.; Zhang, H.; Mao, F. Development of multifunctional pyrimidinylthiourea derivatives as potential anti-Alzheimer agents. J. Med. Chem., 2016, 59(18), 8326-8344.
[http://dx.doi.org/10.1021/acs.jmedchem.6b00636] [PMID: 27552582]
[35]
Kovalevich, J.; Cornec, A.S.; Yao, Y.; James, M.; Crowe, A.; Lee, V.M.Y.; Trojanowski, J.Q.; Smith, A.B., III; Ballatore, C.; Brunden, K.R. Characterization of brain-penetrant pyrimidine-containing molecules with differential microtubule-stabilizing activities developed as potential therapeutic agents for Alzheimers disease and related tauopathies. J. Pharmacol. Exp. Ther., 2016, 357(2), 432-450.
[http://dx.doi.org/10.1124/jpet.115.231175] [PMID: 26980057]
[36]
Li, N.; Wang, Y.; Li, W.; Li, H.; Yang, L.; Wang, J.; Mahdy, H.A.; Mehany, A.B.M.; Jaiash, D.A.; Santali, E.Y.; Eissa, I.H. Screening of some sulfonamide and sulfonylurea derivatives as antialzheimer’s agents targeting BACE1 and PPAR γ. J. Chem., 2020, 2020
[37]
Rehman, T.U.; Khan, I.U.; Ashraf, M.; Tarazi, H.; Riaz, S.; Yar, M. An efficient synthesis of bi -aryl pyrimidine heterocycles: Potential new drug candidates to treat Alzheimer’s disease. Arch. Pharm. (Weinheim), 2017, 350(3-4), 1600304.
[http://dx.doi.org/10.1002/ardp.201600304] [PMID: 28220522]
[38]
Jameel, E.; Meena, P.; Maqbool, M.; Kumar, J.; Ahmed, W.; Mumtazuddin, S.; Tiwari, M.; Hoda, N.; Jayaram, B. Rational design, synthesis and biological screening of triazine-triazolopyrimidine hybrids as multitarget anti-Alzheimer agents. Eur. J. Med. Chem., 2017, 136, 36-51.
[http://dx.doi.org/10.1016/j.ejmech.2017.04.064] [PMID: 28478343]
[39]
Reddy, E.K.; Remya, C.; Sajith, A.M.; Dileep, K.V.; Sadasivan, C.; Anwar, S. Functionalised dihydroazo pyrimidine derivatives from Morita–Baylis–Hillman acetates: Synthesis and studies against acetylcholinesterase as its inhibitors. RSC Advances, 2016, 6, 77431-77439.
[http://dx.doi.org/10.1039/C6RA12507G]
[40]
Jismy, B.; Akssira, M.; Knez, D.; Guillaumet, G.; Gobec, S.; Abarbri, M. Efficient synthesis and preliminary biological evaluations of trifluoromethylated imidazo[1,2- a]pyrimidines and benzimidazo[1,2- a]pyrimidines. New J. Chem., 2019, 43(25), 9961-9968.
[http://dx.doi.org/10.1039/C9NJ01982K]
[41]
Kumar, J.; Gill, A.; Shaikh, M.; Singh, A.; Shandilya, A.; Jameel, E.; Sharma, N.; Mrinal, N.; Hoda, N.; Jayaram, B. Pyrimidine-triazolopyrimidine and pyrimidine-pyridine hybrids as potential acetylcholinesterase inhibitors for Alzheimer’s disease. ChemistrySelect, 2018, 3(2), 736-747.
[http://dx.doi.org/10.1002/slct.201702599]
[42]
Mishra, C.B.; Manral, A.; Kumari, S.; Saini, V.; Tiwari, M. Design, synthesis and evaluation of novel indandione derivatives as multifunctional agents with cholinesterase inhibition, anti-β-amyloid aggregation, antioxidant and neuroprotection properties against Alzheimer’s disease. Bioorg. Med. Chem., 2016, 24(16), 3829-3841.
[http://dx.doi.org/10.1016/j.bmc.2016.06.027] [PMID: 27353888]
[43]
Wang, M.; Qin, H.L.; Leng, J. Ameeduzzafar; Amjad, M.W.; Raja, M.A.G.; Hussain, M.A.; Bukhari, S.N.A. Synthesis and biological evaluation of new tetramethylpyrazine-based chalcone derivatives as potential anti-Alzheimer agents. Chem. Biol. Drug Des., 2018, 92(5), 1859-1866.
[http://dx.doi.org/10.1111/cbdd.13355] [PMID: 29923315]
[44]
Xu, Y.; Wang, H.; Li, X.; Dong, S.; Liu, W.; Gong, Q.; Wang, T.; Tang, Y.; Zhu, J.; Li, J.; Zhang, H.; 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]
[45]
Zribi, L.; Pachòn-Angona, I.; Bautista-Aguilera, Ò.M.; Diez-Iriepa, D.; Marco-Contelles, J.; Ismaili, L.; Iriepa, I.; Chabchoub, F. Triazolopyridopyrimidine: A new scaffold for dual-target small molecules for Alzheimer’s disease therapy. Molecules, 2020, 25(14), 3190.
[http://dx.doi.org/10.3390/molecules25143190] [PMID: 32668671]
[46]
Semenov, V.E.; Zueva, I.V.; Mukhamedyarov, M.A.; Lushchekina, S.V.; Petukhova, E.O.; Gubaidullina, L.M.; Krylova, E.S.; Saifina, L.F.; Lenina, O.A.; Petrov, K.A. Novel acetylcholinesterase inhibitors based on uracil moiety for possible treatment of Alzheimer disease. Molecules, 2020, 25(18), 4191.
[http://dx.doi.org/10.3390/molecules25184191] [PMID: 32932702]
[47]
Semenov, V.E.; Zueva, I.V.; Lushchekina, S.V.; Lenina, O.A.; Gubaidullina, L.M.; Saifina, L.F.; Shulaeva, M.M.; Kayumova, R.M.; Saifina, A.F.; Gubaidullin, A.T.; Kondrashova, S.A.; Latypov, S.K.; Masson, P.; Petrov, K.A. 6-Methyluracil derivatives as peripheral site ligand-hydroxamic acid conjugates: Reactivation for paraoxon-inhibited acetylcholinesterase. Eur. J. Med. Chem., 2020, 185, 111787.
[http://dx.doi.org/10.1016/j.ejmech.2019.111787] [PMID: 31675511]
[48]
Dias, K.S.T.; de Paula, C.T.; dos Santos, T.; Souza, I.N.O.; Boni, M.S.; Guimarães, M.J.R.; da Silva, F.M.R.; Castro, N.G.; Neves, G.A.; Veloso, C.C.; Coelho, M.M.; de Melo, I.S.F.; Giusti, F.C.V.; Giusti-Paiva, A.; da Silva, M.L.; Dardenne, L.E.; Guedes, I.A.; Pruccoli, L.; Morroni, F.; Tarozzi, A.; Viegas, C., Jr Design, synthesis and evaluation of novel feruloyl-donepezil hybrids as potential multitarget drugs for the treatment of Alzheimer’s disease. Eur. J. Med. Chem., 2017, 130, 440-457.
[http://dx.doi.org/10.1016/j.ejmech.2017.02.043] [PMID: 28282613]
[49]
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]
[50]
Sugimoto, H.; Yamanish, 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]
[51]
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]
[52]
Košak, U.; Strašek, N.; Knez, D. Jukič M.; Žakelj, S.; Zahirović A.; Pišlar, A.; Brazzolotto, X.; Nachon, F.; Kos, J.; Gobec, S. N-alkylpiperidine carbamates as potential anti-Alzheimer’s agents. Eur. J. Med. Chem., 2020, 197, 112282.
[http://dx.doi.org/10.1016/j.ejmech.2020.112282] [PMID: 32380361]
[53]
Monjas, L.; Arce, M.P.; León, R.; Egea, J.; Pérez, C.; Villarroya, M.; López, M.G.; Gil, C.; Conde, S.; Rodríguez-Franco, M.I. Enzymatic and solid-phase synthesis of new donepezil-based L- and d-glutamic acid derivatives and their pharmacological evaluation in models related to Alzheimer’s disease and cerebral ischemia. Eur. J. Med. Chem., 2017, 130, 60-72.
[http://dx.doi.org/10.1016/j.ejmech.2017.02.034] [PMID: 28242552]
[54]
Ou, S.; Kwok, K.C. Ferulic acid: Pharmaceutical functions, preparation and applications in foods. J. Sci. Food Agric., 2004, 84(11), 1261-1269.
[http://dx.doi.org/10.1002/jsfa.1873]
[55]
Xu, W.; Wang, X.B.; Wang, Z.M.; Wu, J.J.; Li, F.; Wang, J.; Kong, L.Y. Synthesis and evaluation of donepezil–ferulic acid hybrids as multi-target-directed ligands against Alzheimer’s disease. MedChemComm, 2016, 7(5), 990-998.
[http://dx.doi.org/10.1039/C6MD00053C]
[56]
Benchekroun, M.; Ismaili, L.; Pudlo, M.; Luzet, V.; Gharbi, T.; Refouvelet, B.; Marco-Contelles, J. Donepezil–ferulic acid hybrids as anti-Alzheimer drugs. Future Med. Chem., 2015, 7(1), 15-21.
[http://dx.doi.org/10.4155/fmc.14.148] [PMID: 25582330]
[57]
Estrada, M.; Herrera-Arozamena, C.; Pérez, C.; Viña, D.; Romero, A.; Morales-García, J.A.; Pérez-Castillo, A.; Rodríguez-Franco, M.I. New cinnamic - N-benzylpiperidine and cinnamic - N,N-dibenzyl(N-methyl)amine hybrids as Alzheimer-directed multitarget drugs with antioxidant, cholinergic, neuroprotective and neurogenic properties. Eur. J. Med. Chem., 2016, 121, 376-386.
[http://dx.doi.org/10.1016/j.ejmech.2016.05.055] [PMID: 27267007]
[58]
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]
[59]
Estrada Valencia, M.; Herrera-Arozamena, C.; de Andrés, L.; Pérez, C.; Morales-García, J.A.; Pérez-Castillo, A.; Ramos, E.; Romero, A.; Viña, D.; Yáñez, M.; Laurini, E.; Pricl, S.; Rodríguez-Franco, M.I. Neurogenic and neuroprotective donepezil-flavonoid hybrids with sigma-1 affinity and inhibition of key enzymes in Alzheimer’s disease. Eur. J. Med. Chem., 2018, 156, 534-553.
[http://dx.doi.org/10.1016/j.ejmech.2018.07.026] [PMID: 30025348]
[60]
Asadipour, A.; Alipour, M.; Jafari, M.; Khoobi, M.; Emami, S.; Nadri, H.; Sakhteman, A.; Moradi, A.; Sheibani, V.; Homayouni Moghadam, F.; Shafiee, A.; Foroumadi, A. Novel coumarin-3-carboxamides bearing N-benzylpiperidine moiety as potent acetylcholinesterase inhibitors. Eur. J. Med. Chem., 2013, 70, 623-630.
[http://dx.doi.org/10.1016/j.ejmech.2013.10.024] [PMID: 24211638]
[61]
Cai, P.; Fang, S.Q.; Yang, X.L.; Wu, J.J.; Liu, Q.H.; Hong, H.; Wang, X.B.; Kong, L.Y. Rational design and multibiological profiling of novel donepezil-trolox hybrids against Alzheimer’s disease, with cholinergic, antioxidant, neuroprotective, and cognition enhancing properties. ACS Chem. Neurosci., 2017, 8(11), 2496-2511.
[http://dx.doi.org/10.1021/acschemneuro.7b00257] [PMID: 28806057]
[62]
Asadi, M.; Ebrahimi, M.; Mohammadi-Khanaposhtani, M.; Azizian, H.; Sepehri, S.; Nadri, H.; Biglar, M.; Amanlou, M.; Larijani, B.; Mirzazadeh, R.; Edraki, N.; Mahdavi, M. Design, synthesis, molecular docking, and cholinesterase inhibitory potential of phthalimide‐dithiocarbamate hybrids as new agents for treatment of Alzheimer’s disease. Chem. Biodivers., 2019, 16(11), e1900370.
[http://dx.doi.org/10.1002/cbdv.201900370] [PMID: 31523926]
[63]
Więckowska, A.; Więckowski, K.; Bajda, M.; Brus, B.; Sałat, K.; Czerwińska, P.; Gobec, S.; Filipek, B.; Malawska, B. Synthesis of new N-benzylpiperidine derivatives as cholinesterase inhibitors with β-amyloid anti-aggregation properties and beneficial effects on memory in vivo. Bioorg. Med. Chem., 2015, 23(10), 2445-2457.
[http://dx.doi.org/10.1016/j.bmc.2015.03.051] [PMID: 25868744]
[64]
Li, F.; Wang, Z.M.; Wu, J.J.; Wang, J.; Xie, S.S.; Lan, J.S.; Xu, W.; Kong, L.Y.; Wang, X.B. Synthesis and pharmacological evaluation of donepezil-based agents as new cholinesterase/monoamine oxidase inhibitors for the potential application against Alzheimer’s disease. J. Enzyme Inhib. Med. Chem., 2016, 31(sup3), 41-53.
[http://dx.doi.org/10.1080/14756366.2016.1201814] [PMID: 27384289]
[65]
Samadi, A.; Estrada, M.; Pérez, C.; Rodríguez-Franco, M.I.; Iriepa, I.; Moraleda, I.; Chioua, M.; Marco-Contelles, J. Pyridonepezils, new dual AChE inhibitors as potential drugs for the treatment of Alzheimer’s disease: Synthesis, biological assessment, and molecular modeling. Eur. J. Med. Chem., 2012, 57, 296-301.
[http://dx.doi.org/10.1016/j.ejmech.2012.09.030] [PMID: 23078965]
[66]
Samadi, A.; de la Fuente Revenga, M.; Pérez, C.; Iriepa, I.; Moraleda, I.; Rodríguez-Franco, M.I.; Marco-Contelles, J. Synthesis, pharmacological assessment, and molecular modeling of 6-chloro-pyridonepezils: New dual AChE inhibitors as potential drugs for the treatment of Alzheimer’s disease. Eur. J. Med. Chem., 2013, 67, 64-74.
[http://dx.doi.org/10.1016/j.ejmech.2013.06.021] [PMID: 23838422]
[67]
Zhou, Y.; Sun, W.; Peng, J.; Yan, H.; Zhang, L.; Liu, X.; Zuo, Z. Design, synthesis and biological evaluation of novel copper-chelating acetylcholinesterase inhibitors with pyridine and N-benzylpiperidine fragments. Bioorg. Chem., 2019, 93, 103322.
[http://dx.doi.org/10.1016/j.bioorg.2019.103322] [PMID: 31585263]
[68]
Pudlo, M.; Luzet, V.; Ismaïli, L.; Tomassoli, I.; Iutzeler, A.; Refouvelet, B. Quinolone-benzylpiperidine derivatives as novel acetylcholinesterase inhibitor and antioxidant hybrids for Alzheimer Disease. Bioorg. Med. Chem., 2014, 22(8), 2496-2507.
[http://dx.doi.org/10.1016/j.bmc.2014.02.046] [PMID: 24657052]
[69]
Bautista-Aguilera, O.M.; Esteban, G.; Bolea, I.; Nikolic, K.; Agbaba, D.; Moraleda, I.; Iriepa, I.; Samadi, A.; Soriano, E.; Unzeta, M.; Marco-Contelles, J. Design, synthesis, pharmacological evaluation, QSAR analysis, molecular modeling and ADMET of novel donepezil-indolyl hybrids as multipotent cholinesterase/monoamine oxidase inhibitors for the potential treatment of Alzheimer’s disease. Eur. J. Med. Chem., 2014, 75, 82-95.
[http://dx.doi.org/10.1016/j.ejmech.2013.12.028] [PMID: 24530494]
[70]
Chaves, S.; Resta, S.; Rinaldo, F.; Costa, M.; Josselin, R.; Gwizdala, K.; Piemontese, L.; Capriati, V.; Pereira-Santos, A.R.; Cardoso, S.M.; Santos, M.A. Design, synthesis, and in vitro evaluation of hydroxybenzimidazole-donepezil analogues as multitarget-directed ligands for the treatment of Alzheimer’s disease. Mol, 2020, 25, 985.
[71]
Mo, J.; Chen, T.; Yang, H.; Guo, Y.; Li, Q.; Qiao, Y.; Lin, H.; Feng, F.; Liu, W.; Chen, Y.; Liu, Z.; Sun, H. Design, synthesis, in vitro and in vivo evaluation of benzylpiperidine-linked 1,3-dimethylbenzimidazolinones as cholinesterase inhibitors against Alzheimer’s disease. J. Enzyme Inhib. Med. Chem., 2020, 35(1), 330-343.
[http://dx.doi.org/10.1080/14756366.2019.1699553] [PMID: 31856607]
[72]
Kilic, B.; Gulcan, H.O.; Aksakal, F.; Ercetin, T.; Oruklu, N.; Umit Bagriacik, E.; Dogruer, D.S. Design and synthesis of some new carboxamide and propanamide derivatives bearing phenylpyridazine as a core ring and the investigation of their inhibitory potential on in vitro acetylcholinesterase and butyrylcholinesterase. Bioorg. Chem., 2018, 79, 235-249.
[http://dx.doi.org/10.1016/j.bioorg.2018.05.006] [PMID: 29775949]
[73]
Vila, N.; Besada, P.; Viña, D.; Sturlese, M.; Moro, S.; Terán, C. Synthesis, biological evaluation and molecular modeling studies of phthalazin-1(2H)-one derivatives as novel cholinesterase inhibitors. RSC Advances, 2016, 6(52), 46170-46185.
[http://dx.doi.org/10.1039/C6RA03841G]
[74]
van Greunen, D.G.; Johan van der Westhuizen, C.; Cordier, W.; Nell, M.; Stander, A.; Steenkamp, V.; Panayides, J.L.; Riley, D.L. Novel N-benzylpiperidine carboxamide derivatives as potential cholinesterase inhibitors for the treatment of Alzheimer’s disease. Eur. J. Med. Chem., 2019, 179, 680-693.
[http://dx.doi.org/10.1016/j.ejmech.2019.06.088] [PMID: 31280020]
[75]
de Andrade, P.; Mantoani, S.P.; Gonçalves Nunes, P.S.; Magadán, C.R.; Pérez, C.; Xavier, D.J.; Hojo, E.T.S.; Campillo, N.E.; Martínez, A.; Carvalho, I. Highly potent and selective aryl-1,2,3-triazolyl benzylpiperidine inhibitors toward butyrylcholinesterase in Alzheimer’s disease. Bioorg. Med. Chem., 2019, 27(6), 931-943.
[http://dx.doi.org/10.1016/j.bmc.2018.12.030] [PMID: 30765302]
[76]
El-Sayed, N.A.E.; Farag, A.E.S.; Ezzat, M.A.F.; Akincioglu, H. Gülçin, İ Abou-Seri, S.M. Design, synthesis, in vitro and in vivo evaluation of novel pyrrolizine-based compounds with potential activity as cholinesterase inhibitors and anti-Alzheimer’s agents. Bioorg. Chem., 2019, 93, 103312.
[http://dx.doi.org/10.1016/j.bioorg.2019.103312] [PMID: 31586715]
[77]
Saeedi, M.; Felegari, P.; Iraji, A.; Hariri, R.; Rastegari, A.; Mirfazli, S.S.; Edraki, N.; Firuzi, O.; Mahdavi, M.; Akbarzadeh, T. Novel N ‐benzylpiperidine derivatives of 5‐arylisoxazole‐3‐carboxamides as anti‐Alzheimer’s agents. Arch. Pharm. (Weinheim), 2021, 354(3), 2000258.
[http://dx.doi.org/10.1002/ardp.202000258] [PMID: 33226157]
[78]
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]
[79]
Jiang, X.; Wang, Y.; Liu, C.; Xing, C.; Wang, Y.; Lyu, W.; Wang, S.; Li, Q.; Chen, T.; Chen, Y.; Feng, F.; Liu, W.; Sun, H. Discovery of potent glycogen synthase kinase 3/cholinesterase inhibitors with neuroprotection as potential therapeutic agent for Alzheimer’s disease. Bioorg. Med. Chem., 2021, 30, 115940.
[http://dx.doi.org/10.1016/j.bmc.2020.115940] [PMID: 33340937]
[80]
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]
[81]
Mishra, C.B.; Kumari, S.; Manral, A.; Prakash, A.; Saini, V.; Lynn, A.M.; Tiwari, M. Design, synthesis, in-silico and biological evaluation of novel donepezil derivatives as multi-target-directed ligands for the treatment of Alzheimer’s disease. Eur. J. Med. Chem., 2017, 125, 736-750.
[http://dx.doi.org/10.1016/j.ejmech.2016.09.057] [PMID: 27721157]
[82]
Mohammadi-Farani, A.; Ahmadi, A.; Nadri, H.; Aliabadi, A. Synthesis, docking and acetylcholinesterase inhibitory assessment of 2-(2-(4-Benzylpiperazin-1-yl)ethyl)isoindoline-1,3-dione derivatives with potential anti-Alzheimer effects. Daru, 2013, 21(1), 47.
[http://dx.doi.org/10.1186/2008-2231-21-47] [PMID: 23758724]
[83]
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]
[84]
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]
[85]
Luo, Z.; Liang, L.; Sheng, J.; Pang, Y.; Li, J.; Huang, L.; Li, X. Synthesis and biological evaluation of a new series of Ebselen derivatives as glutathione peroxidase (GPx) mimics and cholinesterase inhibitors against Alzheimer’s disease. Bioorg. Med. Chem., 2014, 22(4), 1355-1361.
[http://dx.doi.org/10.1016/j.bmc.2013.12.066] [PMID: 24461494]
[86]
Gupta, M.; Ojha, M.; Yadav, D.; Pant, S.; Yadav, R. Novel benzylated (pyrrolidin-2-one)/(imidazolidin-2-one) derivatives as potential anti-alzheimer’s agents: Synthesis and pharmacological investigations. ACS Chem. Neurosci., 2020, 11(18), 2849-2860.
[http://dx.doi.org/10.1021/acschemneuro.0c00403] [PMID: 32816447]
[87]
Cai, R.; Wang, L.N.; Fan, J.J.; Geng, S.Q.; Liu, Y.M. New 4-N-phenylaminoquinoline derivatives as antioxidant, metal chelating and cholinesterase inhibitors for Alzheimer’s disease. Bioorg. Chem., 2019, 93, 103328.
[http://dx.doi.org/10.1016/j.bioorg.2019.103328] [PMID: 31600664]
[88]
Özturan Özer, E.; Unsal Tan, O.; Ozadali, K. Küçükkılınç, T.; Balkan, A.; Uçar, G. Synthesis, molecular modeling and evaluation of novel N′-2-(4-benzylpiperidin-/piperazin-1-yl)acylhydrazone derivatives as dual inhibitors for cholinesterases and Aβ aggregation. Bioorg. Med. Chem. Lett., 2013, 23(2), 440-443.
[http://dx.doi.org/10.1016/j.bmcl.2012.11.064] [PMID: 23273219]
[89]
Żurek, 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]
[90]
Wang, Z.M.; Cai, P.; Liu, Q.H.; Xu, D.Q.; Yang, X.L.; Wu, J.J.; Kong, L.Y.; Wang, X.B. Rational modification of donepezil as multifunctional acetylcholinesterase inhibitors for the treatment of Alzheimer’s disease. Eur. J. Med. Chem., 2016, 123, 282-297.
[http://dx.doi.org/10.1016/j.ejmech.2016.07.052] [PMID: 27484514]
[91]
Rosini, M.; Simoni, E.; Caporaso, R.; Basagni, F.; Catanzaro, M.; Abu, I.F.; Fagiani, F.; Fusco, F.; Masuzzo, S.; Albani, D.; Lanni, C.; Mellor, I.R.; Minarini, A. Merging memantine and ferulic acid to probe connections between NMDA receptors, oxidative stress and amyloid-β peptide in Alzheimer’s disease. Eur. J. Med. Chem., 2019, 180, 111-120.
[http://dx.doi.org/10.1016/j.ejmech.2019.07.011] [PMID: 31301562]
[92]
Srivastava, P.; Tripathi, P.N.; Sharma, P.; Shrivastava, S.K. Design, synthesis, and evaluation of novel N-(4-phenoxybenzyl)aniline derivatives targeting acetylcholinesterase, β-amyloid aggregation and oxidative stress to treat Alzheimer’s disease. Bioorg. Med. Chem., 2019, 27(16), 3650-3662.
[http://dx.doi.org/10.1016/j.bmc.2019.07.001] [PMID: 31288978]
[93]
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]
[94]
Pan, T.; Xie, S.; Zhou, Y.; Hu, J.; Luo, H.; Li, X.; Huang, L. Dual functional cholinesterase and PDE4D inhibitors for the treatment of Alzheimer’s disease: Design, synthesis and evaluation of tacrine-pyrazolo[3,4-b]pyridine hybrids. Bioorg. Med. Chem. Lett., 2019, 29(16), 2150-2152.
[http://dx.doi.org/10.1016/j.bmcl.2019.06.056] [PMID: 31281020]
[95]
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]
[96]
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]
[97]
Montanari, S.; Mahmoud, A.M.; Pruccoli, L.; Rabbito, A.; Naldi, M.; Petralla, S.; Moraleda, I.; Bartolini, M.; Monti, B.; Iriepa, I.; Belluti, F.; Gobbi, S.; Di Marzo, V.; Bisi, A.; Tarozzi, A.; Ligresti, A.; Rampa, A. Discovery of novel benzofuran-based compounds with neuroprotective and immunomodulatory properties for Alzheimer’s disease treatment. Eur. J. Med. Chem., 2019, 178, 243-258.
[http://dx.doi.org/10.1016/j.ejmech.2019.05.080] [PMID: 31185414]
[98]
Huang, W.; Liang, M.; Li, Q.; Zheng, X.; Zhang, C.; Wang, Q.; Tang, L.; Zhang, Z.; Wang, B.; Shen, Z. Development of the “hidden” multifunctional agents for Alzheimer’s disease. Eur. J. Med. Chem., 2019, 177, 247-258.
[http://dx.doi.org/10.1016/j.ejmech.2019.05.051] [PMID: 31158742]
[99]
Gießel, J.M.; Loesche, A.; Csuk, R.; Serbian, I. Caffeic acid phenethyl ester (CAPE)-derivatives act as selective inhibitors of acetylcholinesterase. Eur. J. Med. Chem., 2019, 177, 259-268.
[http://dx.doi.org/10.1016/j.ejmech.2019.05.059] [PMID: 31158743]
[100]
Saeed, A.; Mahesar, P.A.; Zaib, S.; Khan, M.S.; Matin, A.; Shahid, M.; Iqbal, J. Synthesis, cytotoxicity and molecular modelling studies of new phenylcinnamide derivatives as potent inhibitors of cholinesterases. Eur. J. Med. Chem., 2014, 78, 43-53.
[http://dx.doi.org/10.1016/j.ejmech.2014.03.015] [PMID: 24675179]
[101]
Chowdhury, S.R.; Gu, J.; Hu, Y.; Wang, J.; Lei, S.; Tavallaie, M.S.; Lam, C.; Lu, D.; Jiang, F.; Fu, L. Synthesis, biological evaluation and molecular modeling of benzofuran piperidine derivatives as Aβ antiaggregant. Eur. J. Med. Chem., 2021, 222, 113541.
[http://dx.doi.org/10.1016/j.ejmech.2021.113541] [PMID: 34116326]
[102]
Lan, J.S.; Hou, J.W.; Liu, Y.; Ding, Y.; Zhang, Y.; Li, L.; Zhang, T. Design, synthesis and evaluation of novel cinnamic acid derivatives bearing N -benzyl pyridinium moiety as multifunctional cholinesterase inhibitors for Alzheimer’s disease. J. Enzyme Inhib. Med. Chem., 2017, 32(1), 776-788.
[http://dx.doi.org/10.1080/14756366.2016.1256883] [PMID: 28585866]
[103]
Li, Q.; Chen, Y.; Xing, S.; Liao, Q.; Xiong, B.; Wang, Y.; Lu, W.; He, S.; Feng, F.; Liu, W.; Chen, Y.; Sun, H. Highly potent and selective butyrylcholinesterase inhibitors for cognitive improvement and neuroprotection. J. Med. Chem., 2021, 64(10), 6856-6876.
[http://dx.doi.org/10.1021/acs.jmedchem.1c00167] [PMID: 33973470]
[104]
Pasieka, A.; Panek, D. Jończyk, J.; Godyń J.; Szałaj, N.; Latacz, G.; Tabor, J.; Mezeiova, E.; Chantegreil, F.; Dias, J.; Knez, D.; Lu, J.; Pi, R.; Korabecny, J.; Brazzolotto, X.; Gobec, S.; Höfner, G.; Wanner, K.; Więckowska, A.; Malawska, B. Discovery of multifunctional anti-Alzheimer’s agents with a unique mechanism of action including inhibition of the enzyme butyrylcholinesterase and γ-aminobutyric acid transporters. Eur. J. Med. Chem., 2021, 218, 113397.
[http://dx.doi.org/10.1016/j.ejmech.2021.113397] [PMID: 33838585]
[105]
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]
[106]
Sadeghian, B.; Sakhteman, A.; Faghih, Z.; Nadri, H.; Edraki, N.; Iraji, A.; Sadeghian, I.; Rezaei, Z.; Sadeghian, B.; Sakhteman, A.; Faghih, Z.; Nadri, H.; Edraki, N.; Iraji, A.; Sadeghian, I.; Rezaei, Z. Design, synthesis and biological activity evaluation of novel carbazole-benzylpiperidine hybrids as potential anti Alzheimer agents. J. Mol. Struct., 2020, 1221, 128793.
[http://dx.doi.org/10.1016/j.molstruc.2020.128793]
[107]
Gorecki, L.; Misiachna, A.; Damborsky, J.; Dolezal, R.; Korabecny, J.; Cejkova, L.; Hakenova, K.; Chvojkova, M.; Karasova, J.Z.; Prchal, L.; Novak, M.; Kolcheva, M.; Kortus, S.; Vales, K.; Horak, M.; Soukup, O. Structure-activity relationships of dually-acting acetylcholinesterase inhibitors derived from tacrine on N-methyl-d-Aspartate receptors. Eur. J. Med. Chem., 2021, 219, 113434.
[http://dx.doi.org/10.1016/j.ejmech.2021.113434] [PMID: 33892271]
[108]
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]
[109]
Ghobadian, R.; Nadri, H.; Moradi, A.; Bukhari, S.N.A.; Mahdavi, M.; Asadi, M.; Akbarzadeh, T.; Khaleghzadeh-Ahangar, H.; Sharifzadeh, M.; Amini, M. Design, synthesis, and biological evaluation of selective and potent carbazole-based butyrylcholinesterase inhibitors. Bioorg. Med. Chem., 2018, 26(17), 4952-4962.
[http://dx.doi.org/10.1016/j.bmc.2018.08.035] [PMID: 30190181]
[110]
Li, Q.; Xing, S.; Chen, Y.; Liao, Q.; Xiong, B.; He, S.; Lu, W.; Liu, Y.; Yang, H.; Li, Q.; Feng, F.; Liu, W.; Chen, Y.; Sun, H. Discovery and biological evaluation of a novel highly potent selective butyrylcholinsterase inhibitor. J. Med. Chem., 2020, 63(17), 10030-10044.
[http://dx.doi.org/10.1021/acs.jmedchem.0c01129] [PMID: 32787113]
[111]
Askin, S.; Tahtaci, H. Türkeş C.; Demir, Y.; Ece, A.; Akalın Çiftçi, G.; Beydemir, Ş. Design, synthesis, characterization, in vitro and in silico evaluation of novel imidazo[2,1-b][1,3,4]thiadiazoles as highly potent acetylcholinesterase and non-classical carbonic anhydrase inhibitors. Bioorg. Chem., 2021, 113, 105009.
[http://dx.doi.org/10.1016/j.bioorg.2021.105009] [PMID: 34052739]
[112]
Kalaycı M.; Türkeş C.; Arslan, M.; Demir, Y.; Beydemir, Ş. Novel benzoic acid derivatives: Synthesis and biological evaluation as multitarget acetylcholinesterase and carbonic anhydrase inhibitors. Arch. Pharm. (Weinheim), 2021, 354(3), 2000282.
[http://dx.doi.org/10.1002/ardp.202000282] [PMID: 33155700]

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